Podcasts about Histone

TWiV reviews new committee of experts to counter vaccine misinformation, resignation of NSF Director, dependence of immune response to rabies virus on the gut microbiome, and a nucleosome switch primes hepatitis B virus infection. Hosts: Vincent Racaniello, Rich Condit, and Angela Mingarelli Subscribe (free): Apple Podcasts, RSS, email Become a patron of TWiV! Links for this episode Support science education at MicrobeTV ASV 2025 Committee of experts to counter vaccine misinformation (Science) NSF Director resigns (Science) Dependence of vaccine immune response on gut microbiome (Cell Host Microbe) Nucleosome switch primes HepB replication (Cell) Letters read on TWiV 1212 Timestamps by Jolene Ramsey. Thanks! Weekly Picks Angela – Wild chimpanzees filmed by scientists bonding over alcoholic fruit Rich – Malcolm Gladwell Revisionist History “The Joe Rogan Intervention” Vincent – Measles Misinformation Is on the Rise — and Americans Are Hearing It, Survey Finds Intro music is by Ronald Jenkees Send your virology questions and comments to twiv@microbe.tv Content in this podcast should not be construed as medical advice.

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body, but how do these cells know what to do? Researchers at UC San Diego and Hebrew University of Jerusalem share an intercontinental effort working to determine just that. Alon Goren and Itamar Simon discuss some of the work they are doing to learn more about the human body beyond the cellular level. [Health and Medicine] [Science] [Show ID: 40516]

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body, but how do these cells know what to do? Researchers at UC San Diego and Hebrew University of Jerusalem share an intercontinental effort working to determine just that. Alon Goren and Itamar Simon discuss some of the work they are doing to learn more about the human body beyond the cellular level. [Health and Medicine] [Science] [Show ID: 40516]

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body, but how do these cells know what to do? Researchers at UC San Diego and Hebrew University of Jerusalem share an intercontinental effort working to determine just that. Alon Goren and Itamar Simon discuss some of the work they are doing to learn more about the human body beyond the cellular level. [Health and Medicine] [Science] [Show ID: 40516]

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body, but how do these cells know what to do? Researchers at UC San Diego and Hebrew University of Jerusalem share an intercontinental effort working to determine just that. Alon Goren and Itamar Simon discuss some of the work they are doing to learn more about the human body beyond the cellular level. [Health and Medicine] [Science] [Show ID: 40516]

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body, but how do these cells know what to do? Researchers at UC San Diego and Hebrew University of Jerusalem share an intercontinental effort working to determine just that. Alon Goren and Itamar Simon discuss some of the work they are doing to learn more about the human body beyond the cellular level. [Health and Medicine] [Science] [Show ID: 40516]

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body, but how do these cells know what to do? Researchers at UC San Diego and Hebrew University of Jerusalem share an intercontinental effort working to determine just that. Alon Goren and Itamar Simon discuss some of the work they are doing to learn more about the human body beyond the cellular level. [Health and Medicine] [Science] [Show ID: 40516]

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body, but how do these cells know what to do? Researchers at UC San Diego and Hebrew University of Jerusalem share an intercontinental effort working to determine just that. Alon Goren and Itamar Simon discuss some of the work they are doing to learn more about the human body beyond the cellular level. [Health and Medicine] [Science] [Show ID: 40516]

In this episode of the Epigenetics Podcast, we talked with Johnathan Whetstine from Fox Chase Cancer Center about his work on how histone demethylases affect gene expression and cancer cell stability. The Interview start by discussing a pivotal paper from Jonathan's lab in 2010, where they identified a role for the KDM4A histone demethylase in replication timing and cell cycle progression. They elaborate on the discoveries made regarding the link between histone marks, replication timing, and gene expression control. Jonathan explains the impact of microRNAs on regulating KDM4A and how protein turnover rates can influence cellular responses to treatments like mTOR inhibitors. Further, they explore the causal relationship between histone marks and replication timing, demonstrating how alterations in epigenetic regulation can affect genome stability. Jonathan shares insights from his latest research on H3K9 methylation balance at the MLL-KM2A locus, elucidating how these epigenetic modifications regulate amplifications and rearrangements in cancer cells. The episode concludes with a discussion on the establishment of the Cancer Epigenetics Institute at Fox Chase Cancer Center, aiming to bridge academia and industry to accelerate translational research in cancer epigenetics.   References Black, J. C., Allen, A., Van Rechem, C., Forbes, E., Longworth, M., Tschöp, K., Rinehart, C., Quiton, J., Walsh, R., Smallwood, A., Dyson, N. J., & Whetstine, J. R. (2010). Conserved antagonism between JMJD2A/KDM4A and HP1γ during cell cycle progression. Molecular cell, 40(5), 736–748. https://doi.org/10.1016/j.molcel.2010.11.008 Mishra, S., Van Rechem, C., Pal, S., Clarke, T. L., Chakraborty, D., Mahan, S. D., Black, J. C., Murphy, S. E., Lawrence, M. S., Daniels, D. L., & Whetstine, J. R. (2018). Cross-talk between Lysine-Modifying Enzymes Controls Site-Specific DNA Amplifications. Cell, 174(4), 803–817.e16. https://doi.org/10.1016/j.cell.2018.06.018 Van Rechem, C., Ji, F., Chakraborty, D., Black, J. C., Sadreyev, R. I., & Whetstine, J. R. (2021). Collective regulation of chromatin modifications predicts replication timing during cell cycle. Cell reports, 37(1), 109799. https://doi.org/10.1016/j.celrep.2021.109799 Gray, Z. H., Chakraborty, D., Duttweiler, R. R., Alekbaeva, G. D., Murphy, S. E., Chetal, K., Ji, F., Ferman, B. I., Honer, M. A., Wang, Z., Myers, C., Sun, R., Kaniskan, H. Ü., Toma, M. M., Bondarenko, E. A., Santoro, J. N., Miranda, C., Dillingham, M. E., Tang, R., Gozani, O., … Whetstine, J. R. (2023). Epigenetic balance ensures mechanistic control of MLL amplification and rearrangement. Cell, 186(21), 4528–4545.e18. https://doi.org/10.1016/j.cell.2023.09.009   Related Episodes The Impact of Chromatin Modifiers on Disease Development and Progression (Capucine van Rechem)   Contact Epigenetics Podcast on X Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Epigenetics Podcast on Threads Active Motif on X Active Motif on LinkedIn Email: podcast@activemotif.com

References Guerra, DJ 2024 Lecture materials --- Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

Nels and Vincent discuss the genome sequence of an ancient wooly mammoth, which shows that the three-dimensional architecture of the DNA can persist after 50,000 years. Hosts: Nels Elde and Vincent Racaniello Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of TWiEVO Links for this episode Join the MicrobeTV Discord server Three dimensional architecture of 50,000 year old wooly mammoth genome (Cell) Timestamps by Jolene Science Picks Nels – Mysterious SARS-CoV-2 variants showing up in sewer samples Vincent – ‘Cocaine sharks' found in waters off Brazil Music on TWiEVO is performed by Trampled by Turtles Send your evolution questions and comments to twievo@microbe.tv

References J Biomed Sci 2017. 24, 63. Cell Death & Disease 2014. volume 5, page e1416 Haematologica. 2022 Mar 1; 107(3):721–732 Nucleic Acids Res. 2022 Jan 7; 50(D1): D413–D420 Oncogene 2017. volume 36, pages 5593–5608 Cell. 2021 Apr 1; 184(7):1790–1803.e17. Van Zant and Collins. 1973. "Tuesday's Gone" Lynyrd Skynyrd. https://youtu.be/LJrFxnvcWhc?si=EoL42Pw72Qe_atsz Lennon-McCartney. 1967. "I am the Walrus" Beatles. [Magical Mystery Tour, lp.] https://youtu.be/Ws5klxbI87I?si=QGe84-nMLK4dqgFy Hayward, J. 1967. "Tuesday Afternoon" [Days of Future Passed lp.] Moody Blues https://youtu.be/jmMPBQ4kYKk?si=FjZfDQ6KwCNecphw Mendelsshon, F. 1842 Wedding March C major op 61. https://youtu.be/Z-yUOBft96Y?si=ldxpuxPYTlAExXez --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

BUFFALO, NY- June 5, 2024 – A new research paper was published in Oncotarget's Volume 15 on June 3, 2024, entitled, “Synergistic cytotoxicity of histone deacetylase and poly-ADP ribose polymerase inhibitors and decitabine in pancreatic cancer cells: Implications for novel therapy.” Histone deacetylase inhibitors (HDACi) can modulate the acetylation status of proteins, influencing the genomic instability exhibited by cancer cells. Poly (ADP ribose) polymerase (PARP) inhibitors (PARPi) have a direct effect on protein poly (ADP-ribosyl)ation, which is important for DNA repair. Decitabine is a nucleoside cytidine analogue, which when phosphorylated gets incorporated into the growing DNA strand, inhibiting methylation and inducing DNA damage by inactivating and trapping DNA methyltransferase on the DNA, thereby activating transcriptionally silenced DNA loci. In this new study, researchers Benigno C. Valdez, Apostolia M. Tsimberidou, Bin Yuan, Yago Nieto, Mehmet A. Baysal, Abhijit Chakraborty, Clark R. Andersen, and Borje S. Andersson from The University of Texas MD Anderson Cancer Center explored various combinations of HDACi and PARPi +/− decitabine (hypomethylating agent) in pancreatic cancer cell lines BxPC-3 and PL45 (wild-type BRCA1 and BRCA2) and Capan-1 (mutated BRCA2). “[...] we explored various combinations of HDACis and PARPis, with or without decitabine, in pancreatic cancer cell lines.” The combination of HDACi (panobinostat or vorinostat) with PARPi (talazoparib or olaparib) resulted in synergistic cytotoxicity in all cell lines tested. The addition of decitabine further increased the synergistic cytotoxicity noted with HDACi and PARPi, triggering apoptosis (evidenced by increased cleavage of caspase 3 and PARP1). The 3-drug combination treatments (vorinostat, talazoparib, and decitabine; vorinostat, olaparib, and decitabine; panobinostat, talazoparib, and decitabine; panobinostat, olaparib, and decitabine) induced more DNA damage (increased phosphorylation of histone 2AX) than the individual drugs and impaired the DNA repair pathways (decreased levels of ATM, BRCA1, and ATRX proteins). The 3-drug combinations also altered the epigenetic regulation of gene expression (NuRD complex subunits, reduced levels). “This is the first study to demonstrate synergistic interactions between the aforementioned agents in pancreatic cancer cell lines and provides preclinical data to design individualized therapeutic approaches with the potential to improve pancreatic cancer treatment outcomes.” DOI - https://doi.org/10.18632/oncotarget.28588 Correspondence to - Apostolia M. Tsimberidou - atsimber@mdanderson.org Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28588 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

In this week's episode we'll learn about fitusiran prophylaxis in patients with hemophilia A or B, with or without inhibitors. Next we'll hear about new findings that heterozygous germline variants in the NBN gene that are linked to increased risk of B-cell acute lymphoblastic leukemia in children. Finally, we'll explore new insights on the histone demethylase PHF8, which has been identified as a master regulator of cell-intrinsic immune responses in acute myeloid leukemia. Featured Articles:Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trialGermline genetic NBN variation and predisposition to B-cell acute lymphoblastic leukemia in children Epigenetic control over the cell-intrinsic immune response antagonizes self-renewal in acute myeloid leukemia

In this episode of the Epigenetics Podcast, we talked with Mark Parthun from Ohio State University about his work on the role of Hat1p in chromatin assembly. Mark Parthun shares insights into his pivotal paper in 2004 that explored the link between type B histone acetyltransferases and chromatin assembly, setting the stage for his current research interests in epigenetics. He highlights the role of HAT1 in acetylating lysines on newly synthesized histones, its involvement in double-strand break repair, and the search for phenotypes associated with HAT1 mutations. The discussion expands to a collaborative research project between two scientists uncovering the roles of HAT1 and NASP as chaperones in chromatin assembly. Transitioning from yeast to mouse models, the team investigated the effects of HAT1 knockout on mouse phenotypes, particularly in lung development and craniofacial morphogenesis. They also explored the impact of histone acetylation on chromatin dynamics and its influence on lifespan, aging processes, and longevity.   References Parthun, M. R., Widom, J., & Gottschling, D. E. (1996). The Major Cytoplasmic Histone Acetyltransferase in Yeast: Links to Chromatin Replication and Histone Metabolism. Cell, 87(1), 85–94. https://doi.org/10.1016/S0092-8674(00)81325-2 Kelly, T. J., Qin, S., Gottschling, D. E., & Parthun, M. R. (2000). Type B histone acetyltransferase Hat1p participates in telomeric silencing. Molecular and cellular biology, 20(19), 7051–7058. https://doi.org/10.1128/MCB.20.19.7051-7058.2000 Ai, X., & Parthun, M. R. (2004). The nuclear Hat1p/Hat2p complex: a molecular link between type B histone acetyltransferases and chromatin assembly. Molecular cell, 14(2), 195–205. https://doi.org/10.1016/s1097-2765(04)00184-4 Nagarajan, P., Ge, Z., Sirbu, B., Doughty, C., Agudelo Garcia, P. A., Schlederer, M., Annunziato, A. T., Cortez, D., Kenner, L., & Parthun, M. R. (2013). Histone acetyl transferase 1 is essential for mammalian development, genome stability, and the processing of newly synthesized histones H3 and H4. PLoS genetics, 9(6), e1003518. https://doi.org/10.1371/journal.pgen.1003518 Agudelo Garcia, P. A., Hoover, M. E., Zhang, P., Nagarajan, P., Freitas, M. A., & Parthun, M. R. (2017). Identification of multiple roles for histone acetyltransferase 1 in replication-coupled chromatin assembly. Nucleic Acids Research, 45(16), 9319–9335. https://doi.org/10.1093/nar/gkx545 Popova, L. V., Nagarajan, P., Lovejoy, C. M., Sunkel, B. D., Gardner, M. L., Wang, M., Freitas, M. A., Stanton, B. Z., & Parthun, M. R. (2021). Epigenetic regulation of nuclear lamina-associated heterochromatin by HAT1 and the acetylation of newly synthesized histones. Nucleic Acids Research, 49(21), 12136–12151. https://doi.org/10.1093/nar/gkab1044   Related Episodes Regulation of Chromatin Organization by Histone Chaperones (Geneviève Almouzni) Effects of Non-Enzymatic Covalent Histone Modifications on Chromatin (Yael David) scDamID, EpiDamID and Lamina Associated Domains (Jop Kind)   Contact Epigenetics Podcast on X Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Epigenetics Podcast on Threads Active Motif on X Active Motif on LinkedIn Email: podcast@activemotif.com

In today's episode, I'm diving into the fascinating topic of how trauma bonds impact not only our psychological well-being but also our genetic coding and physical health. So let's start by understanding that our DNA, our very genetic makeup, is significantly affected by the bonds formed through traumatic experiences. While we often focus on the emotional and mental aspects of trauma, it's vital to recognize that trauma leaves a trace in our brains and bodies.Trauma bonds, especially those formed in relationships, have a profound influence on our limbic system. This part of our brain creates a blueprint of the trauma, which then manifests in our subconscious as an ongoing quest to resolve it. However, our limbic system lacks timestamps, creating an endless loop of unresolved trauma.The brain and body can't distinguish past from present, leading to emotional pain and turmoil experienced long after a relationship ends. Whether the trauma bond was with a romantic partner, family member, or friend, the brain's genetic coding remembers and stores it. This is crucial because our subconscious mind governs 95% of our behaviors, constantly striving to address historical trauma, even if it doesn't know how or when.Chronic stress, triggered by trauma bonds, leads to imbalances in our nervous system, high levels of stress hormones, and physical symptoms like disrupted sleep and weakened immunity. The impact of stress isn't limited to psychological distress; it affects our overall health. The body remains in a perpetual fight-or-flight mode, which can lead to various health issues, including gastrointestinal problems, heart conditions, and even cognitive impairment.Furthermore, trauma bonds influence our genetic coding through epigenetics, altering our gene expression. DNA methylation adds methyl groups to specific genes, making them less active, especially in areas related to emotional regulation and stress response. Histone modification affects the accessibility of genes for transcription, making it difficult for us to regulate emotions, think clearly, and problem-solve during stressful situations.Additionally, trauma bonds may be transmitted across generations, impacting not only our lives but those of our descendants. Inherited genetic coding can predispose future generations to similar emotional struggles and relationship dynamics.The key to breaking free from the grip of trauma bonds is a holistic approach that combines psychological and physical healing. Somatic-based techniques, mindfulness, meditation, and self-compassion can help activate dormant genes, rewire our brains, and regulate our nervous systems.Remember, understanding the deeper meaning of your emotions and addressing the roots of your trauma bonds can pave the way for healing and breaking the cycle. If you have any questions or thoughts about this episode, please reach out to me. Your journey to resolution and healing begins with self-awareness and self-compassion.You can find me on Instagram @dr.sarahalsawy or www.healtraumabonding.comSupport the showSet yourself up for relationship success. Whether you're surviving infidelity, solving relationship problems, improving your relationship, growing your self-worth and confidence amidst a trauma bond, here's the place to be.Helping you to feel relationship empowered and set you up for relationship success.LinkedIn Dr Sarah Alsawy-Davies Instagram @dr.sarahalsawy Website www.healtraumabonding.com

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body. From the skin to the brain, muscles to blood, and everything in between, these countless cells collaborate harmoniously to keep us alive and well, but how do these cells know what to do? When a cell divides, how does it know that it's exact counterpart should do the same thing as the original. Researchers at the Goren Lab at UC San Diego are working to determine just that. They discuss some of the work they are doing to learn more about the human body beyond the cellular level [Health and Medicine] [Science] [Show ID: 38259]

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body. From the skin to the brain, muscles to blood, and everything in between, these countless cells collaborate harmoniously to keep us alive and well, but how do these cells know what to do? When a cell divides, how does it know that it's exact counterpart should do the same thing as the original. Researchers at the Goren Lab at UC San Diego are working to determine just that. They discuss some of the work they are doing to learn more about the human body beyond the cellular level [Health and Medicine] [Science] [Show ID: 38259]

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body. From the skin to the brain, muscles to blood, and everything in between, these countless cells collaborate harmoniously to keep us alive and well, but how do these cells know what to do? When a cell divides, how does it know that it's exact counterpart should do the same thing as the original. Researchers at the Goren Lab at UC San Diego are working to determine just that. They discuss some of the work they are doing to learn more about the human body beyond the cellular level [Health and Medicine] [Science] [Show ID: 38259]

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body. From the skin to the brain, muscles to blood, and everything in between, these countless cells collaborate harmoniously to keep us alive and well, but how do these cells know what to do? When a cell divides, how does it know that it's exact counterpart should do the same thing as the original. Researchers at the Goren Lab at UC San Diego are working to determine just that. They discuss some of the work they are doing to learn more about the human body beyond the cellular level [Health and Medicine] [Science] [Show ID: 38259]

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body. From the skin to the brain, muscles to blood, and everything in between, these countless cells collaborate harmoniously to keep us alive and well, but how do these cells know what to do? When a cell divides, how does it know that it's exact counterpart should do the same thing as the original. Researchers at the Goren Lab at UC San Diego are working to determine just that. They discuss some of the work they are doing to learn more about the human body beyond the cellular level [Health and Medicine] [Science] [Show ID: 38259]

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body. From the skin to the brain, muscles to blood, and everything in between, these countless cells collaborate harmoniously to keep us alive and well, but how do these cells know what to do? When a cell divides, how does it know that it's exact counterpart should do the same thing as the original. Researchers at the Goren Lab at UC San Diego are working to determine just that. They discuss some of the work they are doing to learn more about the human body beyond the cellular level [Health and Medicine] [Science] [Show ID: 38259]

The human body is made up of billions of cells. These cells are the basic building blocks of life, and they work together to form tissues, organs, and systems that enable our body to function and carry out various activities. Each cell has its own specific function and role in maintaining the overall health and functionality of the body. From the skin to the brain, muscles to blood, and everything in between, these countless cells collaborate harmoniously to keep us alive and well, but how do these cells know what to do? When a cell divides, how does it know that it's exact counterpart should do the same thing as the original. Researchers at the Goren Lab at UC San Diego are working to determine just that. They discuss some of the work they are doing to learn more about the human body beyond the cellular level [Health and Medicine] [Science] [Show ID: 38259]

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.04.547746v1?rss=1 Authors: Ly, C. H., Chung, J. D., Nguyen, J. H., Tian, L., Schroeder, J., Knaupp, A. S., Su, S., Trieu, J., Salmi, T. M., Zalcenstein, D., Jabbari, J. S., Boughton, B. A., Cox, A. G., Naik, S. H., Polo, J. M., Ritchie, M. E., Lynch, G. S., Ryall, J. G. Abstract: Skeletal muscle contains a resident population of somatic stem cells capable of both self-renewal and differentiation. The signals that regulate this important decision have yet to be fully elucidated. Here we use metabolomics and mass spectrometry imaging (MSI) to identity a state of localized hyperglycaemia following skeletal muscle injury. We show that committed muscle progenitor cells exhibit an enrichment of glycolytic and TCA cycle genes and that extracellular monosaccharide availability regulates intracellular citrate levels and global histone acetylation. Muscle stem cells exposed to a reduced (or altered) monosaccharide environment demonstrate reduced global histone acetylation and transcription of myogenic determination factors (including myod1). Importantly, reduced monosaccharide availability was linked directly to increased rates of asymmetric division and muscle stem cell self-renewal in regenerating skeletal muscle. Our results reveal an important role for the extracellular metabolic environment in the decision to undergo self-renewal or myogenic commitment during skeletal muscle regeneration. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.02.547417v1?rss=1 Authors: Kato-Inui, T., Ono, T., Miyaoka, Y. Abstract: As a versatile genome editing tool, the CRISPR-Cas9 system induces DNA double-strand breaks at targeted sites to activate mainly two DNA repair pathways: HDR which allows precise editing via recombination with a homologous template DNA, and NHEJ which connects two ends of the broken DNA, which is often accompanied by random insertions and deletions. Therefore, how to enhance HDR while suppressing NHEJ is a key to successful applications that require precise genome editing. Histones are small proteins with a lot of basic amino acids that generate electrostatic affinity to DNA. Since H2A.X is involved in DNA repair processes, we fused H2A.X to Cas9 and found that this fusion protein could improve the HDR/NHEJ ratio. As various post-translational modifications of H2A.X play roles in the regulation of DNA repair, we also fused H2A.X mimicry variants to replicate these post-translational modifications including phosphorylation, methylation, and acetylation. However, none of them were effective to improve the HDR/NHEJ ratio. We further fused other histone variants to Cas9 and found that H2A.1 exhibited the improved HDR/NHEJ ratio better than H2A.X. Thus, the fusion of histone variants to Cas9 is a promising option to enhance precise genome editing. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.24.546372v1?rss=1 Authors: Dasgupta, N., Lei, X., Arnold, R., Teneche, M. G., Miller, K. N., Rajesh, A., Davis, A., Anschau, V., Campos, A. R., Gilson, R., Havas, A., Yin, S., Chua, Z. M., Proulx, J., Alcaraz, M., Rather, M. I., Baeza, J., Schultz, D. C., Berger, S. L., Adams, P. D. Abstract: Cellular senescence, a stable proliferation arrest caused by a range of cellular stresses, is a bona fide cause of cell and tissue aging. As well as proliferation arrest, cell senescence is associated with a potent pro-inflammatory phenotype, the senescence-associated secretory phenotype (SASP). Recent studies have shown the importance of cytoplasmic DNA and chromatin, either reverse transcribed expressed retrotransposons or cytoplasmic chromatin fragments (CCF) expelled from the nucleus, in activation of nuclear SASP gene expression via the cGAS/STING cytoplasmic DNA-sensing pathway. As a source of chronic inflammation, over the long term SASP promotes tissue aging and disease. Thus, it is important to better define the mechanism of SASP activation in senescence. We show here that both the Promyelocytic Leukemia (PML) protein and HIRA histone chaperone are required for SASP expression in senescent cells. PML protein is the key organizer of PML nuclear bodies, nuclear features up to 1 micron in diameter, containing many proteins and previously implicated in diverse cellular processes, including control of cell senescence and cellular intrinsic anti-viral immunity. HIRA is a histone chaperone best known for its ability to incorporate histone variant H3.3 into nuclear chromatin in a DNA replication-independent manner, including in non-proliferating senescent cells. HIRA localizes to PML nuclear bodies in senescent cells. We show that both HIRA and PML are required for activation of NF-kB and SASP. We found that HIRA regulates cytoplasmic NF-kB signaling in senescent cells through the CCF-cGAS-STING-TBK1 pathway. HIRA physically interacts with the autophagy cargo receptor p62 Sequestosome-1 (p62), and HIRA and p62 antagonistically regulate SASP. PML is required to maintain integrity of colocalized HIRA and p62 foci in the cell nucleus. Overall, our findings point to functions for HIRA and PML in coordination of cytoplasmic signalling and nuclear gene expression to regulate inflammation during cell senescence and aging. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

References Nat Protoc. 2017 Nov;12(11):2342-2354 Annual Review of Immunology 2021. Volume 39. pp 279-311 Immunity 2022. Volume 55, Issue 8. Pages 1402-1413.e4 --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.04.539464v1?rss=1 Authors: Al-Kachak, A., Fulton, S. L., Farrelly, L. A., Lepack, A. E., Bastle, R. M., Kong, L., Cathomas, F., Newman, E. L., Menard, C., Ramakrishnan, A., Chan, J. C., Safovich, P., Lyu, Y., Covington, H. E., Shen, L., Gleason, K., Tamminga, C. A., Russo, S. J., Maze, I. Abstract: Background: Major depressive disorder (MDD) is a debilitating illness that affects millions of individuals worldwide. While chronic stress increases incidence levels of MDD, stress-mediated disruptions in brain function that precipitate the disorder remain elusive. Serotonin-associated antidepressants (ADs) remain the first line of therapy for many with MDD, yet low remission rates and delays between treatment and symptomatic alleviation have prompted skepticism regarding precise roles for serotonin in the precipitation of MDD. Our group recently demonstrated that serotonin epigenetically modifies histone proteins (H3K4me3Q5ser) to regulate transcriptional permissiveness in brain. However, this phenomenon has not yet been explored following stress and/or AD exposures. Methods: Here, we employed a combination of genome-wide (ChIP-seq, RNA-seq) and western blotting analyses in dorsal raphe nucleus (DRN) of male and female mice exposed to chronic social defeat stress to examine the impact of stress exposures on H3K4me3Q5ser dynamics in DRN, as well as associations between the mark and stress-induced gene expression. Stress-induced regulation of H3K4me3Q5ser levels were also assessed in the context of AD exposures, and viral-mediated gene therapy was employed to manipulate H3K4me3Q5ser levels to examine the impact of reducing the mark in DRN on stress-associated gene expression and behavior. Results: We found that H3K4me3Q5ser plays important roles in stress-mediated transcriptional plasticity in DRN. Mice exposed to chronic stress displayed dysregulated dynamics of H3K4me3Q5ser in DRN, and viral-mediated attenuation of these dynamics rescued stress-mediated gene expression programs and behavior. Conclusions: These findings establish a neurotransmission-independent role for serotonin in stress-associated transcriptional and behavioral plasticity in DRN. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this episode of the Epigenetics Podcast, we caught up with Sarah Kimmins from Université de Montreal to talk about her work on the epigenetics of human sperm cells. The focus of Sarah Kimmins and her lab is how sperm and offspring health is impacted by the father's environment. The core of this is the sperm epigenome, which has been implicated in complex diseases such as infertility, cancer, diabetes, schizophrenia and autism. The Kimmins lab is interested which players play a role in this and came across the Histone post-translational modification H3K4me3. In this interview we talk about how the father's life choices can impact offspring health, which can also be inherited transgenerationally and how this can be used to develop intervention strategies to improve child and adult health.   References Siklenka, K., Erkek, S., Godmann, M., Lambrot, R., McGraw, S., Lafleur, C., Cohen, T., Xia, J., Suderman, M., Hallett, M., Trasler, J., Peters, A. H., & Kimmins, S. (2015). Disruption of histone methylation in developing sperm impairs offspring health transgenerationally. Science (New York, N.Y.), 350(6261), aab2006. https://doi.org/10.1126/science.aab2006 Lismer, A., Siklenka, K., Lafleur, C., Dumeaux, V., & Kimmins, S. (2020). Sperm histone H3 lysine 4 trimethylation is altered in a genetic mouse model of transgenerational epigenetic inheritance. Nucleic acids research, 48(20), 11380–11393. https://doi.org/10.1093/nar/gkaa712 Lismer, A., Dumeaux, V., Lafleur, C., Lambrot, R., Brind'Amour, J., Lorincz, M. C., & Kimmins, S. (2021). Histone H3 lysine 4 trimethylation in sperm is transmitted to the embryo and associated with diet-induced phenotypes in the offspring. Developmental cell, 56(5), 671–686.e6. https://doi.org/10.1016/j.devcel.2021.01.014   Related Episodes H3K4me3, SET Proteins, Isw1, and their Role in Transcription (Jane Mellor) The Effects of Early Life Stress on Mammalian Development (Catherine J. Peña) DNA Methylation and Mammalian Development (Déborah Bourc'his)   Contact Epigenetics Podcast on Twitter Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Active Motif on Twitter Active Motif on LinkedIn Email: podcast@activemotif.com

References Genes (Basel). 2021 Aug; 12(8): 1118. Nature Reviews Immunology 2018. volume 18, pages 617–634. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

References Nature Reviews Immunology volume 18, pages 617–634 (2018) Genes (Basel). 2021 Aug; 12(8): 1118. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

References Cell Death & Differentiation 2020.27: 3374–3385 Cell Death & Differentiation 2019. 26: 1501–1515 Cancers 2020, 12(8), 2137. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

References Cell Research. 2022. volume 32, pages 687–690 . --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

References Hum Genomics. 2021; 15: 24 JCI Insight. 2020 Sep 3;5(17):e138443 Nature Reviews Genetics volume 14, pages 204–220 (2013) --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Reference JCI Insight . 2020 Sep 3;5(17):e138443 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

References Stem Cell Res Ther. 2021; 12: 163 Biomedicines. 2021 Nov; 9(11): 1666 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

References The Journal of Biological Chemistry16/2/2018293: 2422-2437. Anal Cell Pathol (Amst). 2018; 2018: 787.1814 Nature Reviews Drug Discovery. Sep2014, Vol. 13 Issue 9, p673-691 J Cancer Res Clin Oncol. 2018; 144(6): 1065–1077. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

References J Cancer Res Clin Oncol. 2018; 144(6): 1065–1077 Nature Reviews Drug Discovery. Sep2014, Vol. 13 Issue 9, p673-691 Anal Cell Pathol (Amst). 2018; 2018: 787.1814 The Journal of Biological Chemistry 16/2/2018 293: 2422-2437. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Listen to a blog summary of a recently published research paper in Volume 13 of Oncotarget, entitled, "HDAC inhibitors suppress protein poly(ADP-ribosyl)ation and DNA repair protein levels and phosphorylation status in hematologic cancer cells: implications for their use in combination with PARP inhibitors and chemotherapeutic drugs." _______________________________________ Chromatin constitutes chromosomes in eukaryotic cells and comprises DNA and proteins. Chromosomes produce proteins and enzymes that are essential for cellular function and maintenance, including DNA repair. A critical process for DNA repair is poly(ADP-ribosyl)ation, or PARylation. PARylation is triggered by poly(ADP ribose) polymerase (PARP) enzymes. When DNA becomes damaged, PARP enzymes bind to the damaged location in the cell. In cancer cells, however, this natural process can be counterproductive in respect to cancer treatment. PARylation can produce DNA repair mechanisms in cancer cells that can lead to the evasion of cell death, and even drug resistance. Inhibiting PARylation may be a viable therapeutic strategy for cancer treatment. Histones, the main proteins that constitute chromatin, undergo post-translational modifications that regulate gene expression. Histone acetylation is an important epigenetic process that affects gene expression by relaxing the chromatin structure, making chromatin remodeling more feasible. Histone deacetylases (HDACs) are enzymes that can have the opposite effect. Histone deacetylation makes the chromatin more compact and difficult to remodel. The overexpression of HDAC has also been associated with tumorigenesis. Histone deacetylase inhibitors (HDACi) are a class of therapeutics that have shown promise in the treatment of hematologic malignancies (blood cancer) and solid tumors. In a new study, researchers Benigno C. Valdez, Yago Nieto, Bin Yuan, David Murray, and Borje S. Andersson from the Department of Stem Cell Transplantation and Cellular Therapy at the University of Texas MD Anderson Cancer Center and the Cross Cancer Institute's Department of Experimental Oncology at the University of Alberta investigate the efficacy of HDACi in combination with PARP inhibitors (PARPi) and chemotherapeutic drugs to treat hematologic cancer. On October 14, 2022, their research paper was published in Volume 13 of Oncotarget, entitled, “HDAC inhibitors suppress protein poly(ADP-ribosyl)ation and DNA repair protein levels and phosphorylation status in hematologic cancer cells: implications for their use in combination with PARP inhibitors and chemotherapeutic drugs.” Full blog - https://www.oncotarget.org/2022/10/19/synergy-of-hdaci-parpi-and-chemotherapeutics-against-blood-cancer/ DOI - https://doi.org/10.18632/oncotarget.28278 Correspondence to - Benigno C. Valdez - bvaldez@mdanderson.org Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28278 Keywords - poly(ADP-ribosyl)ation, HDAC inhibitors, PARP inhibitors, chemotherapy, hematologic malignancy About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

In this episode of the Epigenetics Podcast, we caught up with Nada Jabado from McGill University to talk about her work on oncohistones as drivers of Pediatric Brain Tumors. Nada Jabado and her team were amongst the first to identify mutations in Histone 3.3 Tails which lead to differentially remodeled chromatin in pediatric glioblastoma. Mutations that occur include the Lysine at position 27 and the Glycine at position 34. If those residues are mutated it will influence the equilibrium of chromatin associated proteins like the Polycomb Repressive Complex (PRC) and hence domains of heterochromatin will be shifted. This, in turn, will lead to differential gene expression and development of developmental disorders or cancer.   References Schwartzentruber, J., Korshunov, A., Liu, X. Y., Jones, D. T., Pfaff, E., Jacob, K., Sturm, D., Fontebasso, A. M., Quang, D. A., Tönjes, M., Hovestadt, V., Albrecht, S., Kool, M., Nantel, A., Konermann, C., Lindroth, A., Jäger, N., Rausch, T., Ryzhova, M., Korbel, J. O., … Jabado, N. (2012). Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature, 482(7384), 226–231. https://doi.org/10.1038/nature10833 Kleinman, C. L., Gerges, N., Papillon-Cavanagh, S., Sin-Chan, P., Pramatarova, A., Quang, D. A., Adoue, V., Busche, S., Caron, M., Djambazian, H., Bemmo, A., Fontebasso, A. M., Spence, T., Schwartzentruber, J., Albrecht, S., Hauser, P., Garami, M., Klekner, A., Bognar, L., Montes, J. L., … Jabado, N. (2014). Fusion of TTYH1 with the C19MC microRNA cluster drives expression of a brain-specific DNMT3B isoform in the embryonal brain tumor ETMR. Nature genetics, 46(1), 39–44. https://doi.org/10.1038/ng.2849 Papillon-Cavanagh, S., Lu, C., Gayden, T., Mikael, L. G., Bechet, D., Karamboulas, C., Ailles, L., Karamchandani, J., Marchione, D. M., Garcia, B. A., Weinreb, I., Goldstein, D., Lewis, P. W., Dancu, O. M., Dhaliwal, S., Stecho, W., Howlett, C. J., Mymryk, J. S., Barrett, J. W., Nichols, A. C., … Jabado, N. (2017). Impaired H3K36 methylation defines a subset of head and neck squamous cell carcinomas. Nature genetics, 49(2), 180–185. https://doi.org/10.1038/ng.3757 Chen, C., Deshmukh, S., Jessa, S., Hadjadj, D., Lisi, V., Andrade, A. F., Faury, D., Jawhar, W., Dali, R., Suzuki, H., Pathania, M., A, D., Dubois, F., Woodward, E., Hébert, S., Coutelier, M., Karamchandani, J., Albrecht, S., Brandner, S., De Jay, N., … Jabado, N. (2020). Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis. Cell, 183(6), 1617–1633.e22. https://doi.org/10.1016/j.cell.2020.11.012 Chaouch, A., Berlandi, J., Chen, C., Frey, F., Badini, S., Harutyunyan, A. S., Chen, X., Krug, B., Hébert, S., Jeibmann, A., Lu, C., Kleinman, C. L., Hasselblatt, M., Lasko, P., Shirinian, M., & Jabado, N. (2021). Histone H3.3 K27M and K36M mutations de-repress transposable elements through perturbation of antagonistic chromatin marks. Molecular cell, 81(23), 4876–4890.e7. https://doi.org/10.1016/j.molcel.2021.10.008   Related Episodes Cancer and Epigenetics (David Jones) Epigenetics & Glioblastoma: New Approaches to Treat Brain Cancer (Lucy Stead) Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

A new research paper was published in Aging (Aging-US) on the cover of Volume 14, Issue 12, entitled, “Time makes histone H3 modifications drift in mouse liver.” Aging is known to involve epigenetic histone modifications, which are associated with transcriptional changes, occurring throughout the entire lifespan of an individual. “So far, no study discloses any drift of histone marks in mammals which is time-dependent or influenced by pro-longevity caloric restriction treatment.” To detect the epigenetic drift of time passing, researchers—from Istituto di Ricovero e Cura a Carattere Scientifico, University of Urbino ‘Carlo Bo', University of Milan, and University of Padua—determined the genome-wide distributions of mono- and tri-methylated lysine 4 and acetylated and tri-methylated lysine 27 of histone H3 in the livers of healthy 3, 6 and 12 months old C57BL/6 mice. “In this study, we used chromatin immunoprecipitation sequencing technology to acquire 108 high-resolution profiles of H3K4me3, H3K4me1, H3K27me3 and H3K27ac from the livers of mice aged between 3 months and 12 months and fed 30% caloric restriction diet (CR) or standard diet (SD).” The comparison of different age profiles of histone H3 marks revealed global redistribution of histone H3 modifications with time, in particular in intergenic regions and near transcription start sites, as well as altered correlation between the profiles of different histone modifications. Moreover, feeding mice with caloric restriction diet, a treatment known to retard aging, reduced the extent of changes occurring during the first year of life in these genomic regions. “In conclusion, while our data do not establish that the observed changes in H3 modification are causally involved in aging, they indicate age, buffered by caloric restriction, releases the histone H3 marking process of transcriptional suppression in gene desert regions of mouse liver genome most of which remain to be functionally understood.” DOI: https://doi.org/10.18632/aging.204107 Corresponding Author: Marco Giorgio - marco.giorgio@unipd.it Keywords: epigenetics, aging, histones, ChIP-seq, diet Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204107 About Aging-US: Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Follow Aging on social media: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com

References Sci Signal. 2016 Aug 23; 9(442): ra83. Dr Guerra's Neuroscience lectures --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

BUFFALO, NY- June 15, 2022 – A new research paper was published in Aging (Aging-US) on the cover of Volume 14, Issue 11, entitled, “Histone deacetylase 4 reverses cellular senescence via DDIT4 in dermal fibroblasts.” Researchers—from Seoul National University, Seoul National University College of Medicine, Seoul National University Graduate School, and Daegu Gyeongbuk Institute of Science and Technology (DGIST)—previously demonstrated that histone deacetylase 4 (HDAC4) is consistently downregulated in aged and ultraviolet (UV)-irradiated human skin. However, there is little research on how HDAC4 causes skin aging. “To elucidate the potential role of HDAC4 in the regulation of cellular senescence and skin aging, we established oxidative stress- and UV-induced cellular senescence models using primary human dermal fibroblasts (HDFs).” After overexpression or knockdown of HDAC4 in primary HDFs, RNA sequencing identified candidate molecular targets of HDAC4. “Integrative analyses of our current and public mRNA expression profiles identified DNA damage-inducible transcript 4 (DDIT4) as a critical senescence-associated factor regulated by HDAC4.” Full press release - https://aging-us.net/2022/06/15/aging-us-ddit4-identified-as-candidate-target-of-hdac4-associated-skin-aging/ DOI: https://doi.org/10.18632/aging.204118 Corresponding Authors: Daehee Hwang - daehee@snu.ac.kr, Dong Hun Lee - ivymed27@snu.ac.kr, Jin Ho Chung - jhchung@snu.ac.kr Keywords: cellular senescence, DNA damage-inducible transcript 4, histone deacetylase 4, oxidative stress, ultraviolet light Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204118 About Aging-US: Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Follow Aging on social media: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com.

In this episode of the Epigenetics Podcast, we caught up with Ian Maze from Ichan School of Medicine at Mount Sinai and a Howard Hughes Medical Institute (HHMI) Investigator to talk about his work on the role of histone dopaminylation and serotinylation in neuronal plasticity. The Maze group focuses on understanding the complex interplay between chromatin regulatory mechanisms in brain and neuronal plasticity. The lab places an emphasis on psychiatric disorders associated with monoaminergic (e.g., serotonin, dopamine, etc.) dysfunction, such as major depressive disorder and drug addiction. In particular the Maze team has investigated cocaine addiction and its effect on chromatin by serotonylation and dopaminylation of Histone H3 Tails.   References Maze, I., Covington, H. E., Dietz, D. M., LaPlant, Q., Renthal, W., Russo, S. J., Mechanic, M., Mouzon, E., Neve, R. L., Haggarty, S. J., Ren, Y., Sampath, S. C., Hurd, Y. L., Greengard, P., Tarakhovsky, A., Schaefer, A., & Nestler, E. J. (2010). Essential Role of the Histone Methyltransferase G9a in Cocaine-Induced Plasticity. Science, 327(5962), 213–216. https://doi.org/10.1126/science.1179438 Farrelly, L. A., Thompson, R. E., Zhao, S., Lepack, A. E., Lyu, Y., Bhanu, N. V., Zhang, B., Loh, Y.-H. E., Ramakrishnan, A., Vadodaria, K. C., Heard, K. J., Erikson, G., Nakadai, T., Bastle, R. M., Lukasak, B. J., Zebroski, H., Alenina, N., Bader, M., Berton, O., … Maze, I. (2019). Histone serotonylation is a permissive modification that enhances TFIID binding to H3K4me3. Nature, 567(7749), 535–539. https://doi.org/10.1038/s41586-019-1024-7 Lepack, A. E., Werner, C. T., Stewart, A. F., Fulton, S. L., Zhong, P., Farrelly, L. A., Smith, A. C. W., Ramakrishnan, A., Lyu, Y., Bastle, R. M., Martin, J. A., Mitra, S., O'Connor, R. M., Wang, Z.-J., Molina, H., Turecki, G., Shen, L., Yan, Z., Calipari, E. S., … Maze, I. (2020). Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking. Science, 368(6487), 197–201. https://doi.org/10.1126/science.aaw8806   Related Episodes Development of Integrative Machine Learning Tools for Neurodegenerative Diseases (Enrico Glaab) Epigenetic Influence on Memory Formation and Inheritance (Isabelle Mansuy) CpG Islands, DNA Methylation, and Disease (Sir Adrian Bird)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

The experimental compound, called GSK-LSD1, enhances social preferences and reduces repetitive grooming in mice, according to a new study. The post Histone-modifying drug improves autism-like behaviors in mice appeared first on Spectrum | Autism Research News.

The experimental compound, called GSK-LSD1, enhances social preferences and reduces repetitive grooming in mice, according to a new study.

The experimental compound, called GSK-LSD1, enhances social preferences and reduces repetitive grooming in mice, according to a new study.

REFERENCED STUDIES FOR ANDROGENETIC ALOPECIA Silva et al (starts at 1:10). Randomized clinical trial of low-dose oral minoxidil for the treatment of female pattern hair Loss: 0.25 mg versus 1 mg. Journal of the American Academy of Dermatology;  Online Jan 2022. Therianou et al (starts at 3;18). How Safe Is Prescribing Oral Minoxidil in Patients Allergic to Topical Minoxidil? Journal of the American Academy of Dermatology. J Am Acad Dermatol Feb 2022. James JF et al. (starts at 4:51) Efficacy and safety profile of oral spironolactone use for androgenic alopecia: A systematic review. J Am Acad Dermatol. Feb 2022 Plante et al (starts at 8:05). The Need for Potassium Monitoring in Women on Spironolactone for Dermatologic Conditions. J Am Acad Dermatol. 2022 Jan 21 Online;S0190-9622(22)00081-0. Özcan D (starts at 10:59). Pediatric androgenetic alopecia: a retrospective review of clinical  characteristics, hormonal assays and   metabolic syndrome risk factors in 23 patients An Bras Dermatol. 2022 Jan 12; online Zong et al (starts at 14:40). Prevalence of ocular anomalies is increased in women with polycystic ovary syndrome-exploration of association with PAX6 genotype. Ophthalmic Genetics. 2022 Jan 11;1-4. Online Deng et al (starts at 15:51). Androgen receptor mediated paracrine signaling induces regression of blood vessels in the dermal papilla in androgenetic alopecia. J Invest Dermatol. Jan 2022 online Li K et al (starts at 18:48). Association of fibrosis in the bulge portion with hair follicle miniaturization in androgenetic alopecia. J Am Acad Dermatol 2022; Jan;86(1):213-215.   REFERENCED STUDIES FOR ALOPECIA AREATA Di Fillipo et al (starts at 22:14). Efficacy of 308-nm excimer therapy in alopecia areata: a retrospective study with long-term follow-up Photodermatol Photoimmunol Photomed 2022 Jan 21.  online. Ting H-C et al (starts at 25:30). Association between alopecia areata and retinal diseases: A nationwide population-based cohort study. J Am Acad Dermatol  2021 Nov 1; online Abdelkader HA et al (starts at 26:24). Histone deacetylase 1 in patients with alopecia areata and acne vulgaris: An epigenetic alteration. Australas J Dermatol. 2022 Jan 25. Online.

Welcome to the final episode of season 1!!! In this episode we tackle the following classes: PI3K inhibitors, mTOR inhibitors, Proteosome inhibitors, Histone deacetylase inhibitors, DNA Methylation inhibitors, Hedgehog pathway blockers, and CAR T cell therapy. What an exciting group of target therapies, novel ways to fight cancer that are really fascinating.

My AP Biology Thoughts  Unit 5 HeredityWelcome to My AP Biology Thoughts podcast, my name is Helena Holley and I am your host for episode #109 called Unit 6 gene expression and regulation: Regulation of gene expression. Today we will be discussing the mechanism of gene expressions and regulation in Eukaryotes and Prokaryotes. Segment 1: Introduction to Gene Expression and Regulation Gene expression and its regulation and control is essential for cell specialization in Eukaryotes. All cells have the same information, however their differences in function come from which genes they express. As you go through development cells are differentiated. The way this happens is by specific transcription factors and translation controls that tell the cells which genes they are expressing as you develop. Your basic genetics are not the only thing that determines which genes are expressed, epigenetics also plays a role. Certain environmental factors that occur in a parents lifetime can alter the gene expression of offspring. This happens when there are changes in the parents' cells that undergo meiosis to produce gametes. Examples of this include DNA methylation and histone modification. While I was just discussing eukaryotes above, gene expression and regulation is also important in prokaryotes, which I will discuss more later.  Segment 2: More About Gene Expression and RegulationThere are various ways in which gene expression is regulated in Eukaryotes. One regulation method is determined by how tightly DNA is wrapped around Histone proteins. The tighter the DNA is wrapped, the harder it is for transcription to take place, and certain enzymes can alter how tight or loose it is wrapped depending on what needs to happen. There are also chromatin-modifying enzymes that can make the DNA more or less accessible. Another regulatory factor is the Control elements which are regulatory sequences on DNA that control the expression of proteins. Alternative RNA splicing helps to regulate post transcription, as it produces different mRNA from the same gene. Another useful method is mRNA degradation which is used to break down mRNA if the protein is not needed to be expressed anymore. Finally, various regulatory proteins can block initiation of translation if that is needed. It is important to note that mRNA is not the only type of RNA used for regulation, and there are various types of non-coding RNA that have different functions in regulation of gene expression. In prokaryotes there are repressible and inducible operons. The repressible operon genes are able to be silenced, and the inducible operon genes are able to be turned on. This function of these operons is important in gene regulation because if a repressible operon is absent, the repressor is inactive and the operon will be produced. When too much of a repressible operon is in the cell, it will bind to the repressor which will bind to the operator, preventing any more from being produced. For inducible operons, the process works essentially the opposite of the repressible operons (so briefly the repressor is active when there is an absence of lac operon, and it is inactive when there is presence lac operon).  Segment 3: Connection to the CourseGene expression and regulation is important because any errors in regulation can lead to developmental problems. For example, If the tumor suppressor gene is silenced due DNA methylation occurring in the parent, the offspring would be very susceptible to cancer and disease. Another reason why the regulation of expression of genes is important is because not having all genes turned on all the time, conserves a lot of energy and space. It is a lot more efficient to only turn on genes when they are required. Additionally, if every gene was being expressed, cells would have to be much larger because DNA has to be unwound in order to transcribe and translate it.  Thank you for listening to this episode of My AP Biology...