Podcasts about hp1

Fr. Éamonn Bourke and Kris McGregor discuss the why, how, and what of "prayer."  In this episode, they explore the nature of prayer and responding to the call of relationship with God. The post HP1 – What is Prayer? – The Heart of Prayer with Fr. Éamonn Bourke – Discerning Hearts Podcast appeared first on Discerning Hearts Catholic Podcasts.

In this installment of the Longevity & Aging Series, Dr. Julia Sidorova from the Department of Laboratory Medicine and Pathology at the University of Washington (Seattle, WA) joined host Dr. Evgeniy Galimov to discuss her co-authored research paper from Volume 16, Issue 20 of Aging (Aging-US), titled “Werner syndrome RECQ helicase participates in and directs maintenance of the protein complexes of constitutive heterochromatin in proliferating human cells.” DOI - https://doi.org/10.18632/aging.206132 Corresponding Author - Julia M. Sidorova - julias@uw.edu Video interview - https://www.youtube.com/watch?v=3yn8O-JA6GE Abstract Werner syndrome of premature aging is caused by mutations in the WRN RECQ helicase/exonuclease, which functions in DNA replication, repair, transcription, and telomere maintenance. How the loss of WRN accelerates aging is not understood in full. Here we show that WRN is necessary for optimal constitutive heterochromatin levels in proliferating human fibroblasts. Locally, WRN deficiency derepresses SATII pericentromeric satellite repeats but does not reduce replication fork progression on SATII repeats. Globally, WRN loss reduces a subset of protein-protein interactions responsible for the organization of constitutive heterochromatin in the nucleus, namely, the interactions involving Lamin B1 and Lamin B receptor, LBR. Both the mRNA level and subcellular distribution of LBR are affected by WRN deficiency, and unlike the former, the latter phenotype does not require WRN catalytic activities. The phenotypes of heterochromatin disruption seen in WRN-deficient proliferating fibroblasts are also observed in WRN-proficient fibroblasts undergoing replicative or oncogene-induced senescence. WRN interacts with histone deacetylase 2, HDAC2; WRN/HDAC2 association is mediated by heterochromatin protein alpha, HP1α, and WRN complexes with HP1α and HDAC2 are downregulated in senescing cells. The data suggest that the effect of WRN loss on heterochromatin is separable from senescence program, but mimics at least some of the heterochromatin changes associated with it. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206132 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Werner progeria, heterochromatin, senescence, nuclear lamina, satellite repeats About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

In this episode of the Epigenetics Podcast, we talked with Geeta Narlikar from UCSF about her work on chromatin remodeling, Heterochromatin Protein 1, and the molecular mechanisms that influence the genome. The conversation starts with a pivotal paper from the early days of Dr. Narlikars research career, titled "Distinct Strategies to Make Nucleosomal DNA Accessible," focused on two ATP-dependent remodelers, BRG1 and SNF2H. Here, she notes that while both enzymes operate similarly, they generate different outputs and play distinct biological roles within the cell. The research revealed that BRG1 is more aggressive in altering nucleosome configuration, aligning with its role in transcription activation, while SNF2H showed a more refined approach in the formation of heterochromatin. Transitioning to her work at UCSF, she emphasized the importance of collaboration and mentoring within a research group. Her focus then shifted towards the ACF ATP-dependent chromatin assembly factor, hypothesizing how ACF measures nucleosome distance—an inquiry that led to exciting insights regarding dynamic enzyme behavior. This includes findings that ACF operates not through a static ruler mechanism but rather through a kinetic mechanism, thus continuously adjusting nucleosome positioning based on DNA length during chromatin assembly. Dr. Narlikar also delved into her studies on heterochromatin protein 1 (HP1), highlighting how HP1 recognizes methylation marks and assembles on chromatin to facilitate gene silencing. This segment of the discussion underscored her shift to studying phase separation and its implications in the organization of chromatin. Notably, her lab made significant advancements in understanding how HP1 forms phase-separated droplets, a finding that was independently corroborated by other laboratories, demonstrating the utility of collaborative scientific inquiry. In discussing the nuances of chromatin dynamics, Dr. Narlikar also introduced her investigations into the INO80 complex, detailing its distinct mechanism for nucleosome movement compared to other remodelers. Each remodeling complex, as she elucidated, has unique catalytic capabilities while still utilizing similar biochemical foundations, highlighting the diverse regulatory roles these proteins play within cells.   References Racki LR, Yang JG, Naber N, Partensky PD, Acevedo A, Purcell TJ, Cooke R, Cheng Y, Narlikar GJ. The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes. Nature. 2009 Dec 24;462(7276):1016-21. doi: 10.1038/nature08621. PMID: 20033039; PMCID: PMC2869534. Canzio D, Liao M, Naber N, Pate E, Larson A, Wu S, Marina DB, Garcia JF, Madhani HD, Cooke R, Schuck P, Cheng Y, Narlikar GJ. A conformational switch in HP1 releases auto-inhibition to drive heterochromatin assembly. Nature. 2013 Apr 18;496(7445):377-81. doi: 10.1038/nature12032. Epub 2013 Mar 13. PMID: 23485968; PMCID: PMC3907283. Sinha KK, Gross JD, Narlikar GJ. Distortion of histone octamer core promotes nucleosome mobilization by a chromatin remodeler. Science. 2017 Jan 20;355(6322):eaaa3761. doi: 10.1126/science.aaa3761. PMID: 28104838; PMCID: PMC5656449. Larson AG, Elnatan D, Keenen MM, Trnka MJ, Johnston JB, Burlingame AL, Agard DA, Redding S, Narlikar GJ. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature. 2017 Jul 13;547(7662):236-240. doi: 10.1038/nature22822. Epub 2017 Jun 21. PMID: 28636604; PMCID: PMC5606208. Sanulli S, Trnka MJ, Dharmarajan V, Tibble RW, Pascal BD, Burlingame AL, Griffin PR, Gross JD, Narlikar GJ. HP1 reshapes nucleosome core to promote phase separation of heterochromatin. Nature. 2019 Nov;575(7782):390-394. doi: 10.1038/s41586-019-1669-2. Epub 2019 Oct 16. PMID: 31618757; PMCID: PMC7039410.   Related Episodes Enhancers and Chromatin Remodeling in Mammary Gland Development (Camila dos Santos) Heterochromatin Protein 1 and its Influence on the Structure of Chromatin (Serena Sanulli) Heterochromatin and Phase Separation (Gary Karpen)   Contact Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Dr. Stefan Dillinger on LinkedIn Active Motif on LinkedIn Active Motif on Bluesky Email: podcast@activemotif.com

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

Durant cet épisode, Coach Frank cherche à comprendre la dynamique des équipes et le leadership avec Olivier Doucet, Ph. D., et Félix Bélanger, M. Sc. À propos de nos invités: Olivier Doucet: Olivier Doucet (MBA, Ph.D., CRHA) est professeur titulaire et directeur associé au Pôle sports à HEC Montréal. Il enseigne la gestion de la performance et des talents des employés dans divers programmes. À travers ses recherches, il s'intéresse à l'efficacité des saines pratiques de gestion de la performance, les compétences managériales des gestionnaires et la mobilisation des employés. Il aborde ces thématiques en regard de leur dynamique dans les relations gestionnaire-employé, coach-athlète, ainsi que dans les équipes de travail et sportives. Il a formé des centaines de gestionnaires dans différents pays et il accompagné plusieurs entreprises dans la mise en place de pratiques novatrices de gestion de performance. Il est auteur de plus de 35 articles scientifiques, ouvrages et chapitres de livres. Pour rejoindre Olivier: olivier.doucet@hec.ca Félix Bélanger: Diplômé de l'Université du Québec à Trois-Rivières (UQTR), Félix Bélanger se spécialise dans les dynamiques d'équipes sportives et en sciences de la gestion; sa maîtrise porte d'ailleurs sur les formes collectives de leadership dans les équipes sportives. Comme entraîneur, Félix cumule plusieurs années d'expériences auprès de la franchise des Estacades de la Mauricie de la LHEQ. Il est aujourd'hui entraîneur adjoint pour les Dragons du Collège Laflèche, au niveau collégial D1 du RSEQ. Détenteur de la formation HP1 depuis 2014, Félix Bélanger travaille aussi avec le Pôle Sports du HEC Montréal afin d'améliorer la formation en matière de gestion des équipes pour les entraîneur(e)s de hockey au Québec. Au sein de la Fédération, il a par ailleurs présenté diverses conférences sur le leadership. Pour rejoindre Félix: felix.belanger1@uqtr.ca Pour nous rejoindre par courriel: info@tresbonpoint.com Pour en savoir plus sur nos services: https://tresbonpoint.com/contact NOTES D'ÉMISSION Introduction de Olivier Doucet et Félix Bélanger et qu'est-ce qu'ils veulent ressortir et soutenir du podcast. (0:05) Une bonne forme de leadership et le «followership ». (6:53) Le leadership est processuel. (9:15) Collaboration et le projet du leadership partagé. (10:40) C'est quoi les ramifications et conclusions qui sortent du leadership partagé? (15:04) Élargir le leadership. (21:51) Citation : « Il faut que tu emmènes ta game dans la game ». (24 :28) Un coach qui a beaucoup de joueurs qui prennent l'autonomie : reconnaître les forces et les faiblesses. (26:19) Le leadership partagé dans le sport. (31:08) Les catégorisations. (34:15) Collecte de données dans le projet avec Hockey Québec. (37:04) Qu'est ce qu'on devrait voir comme résultat en essayant les choses mentionnés dans les données? (40:40) Comment éduquer les jeunes sur le leadership. (44:15) Comment faire le parallèle entre la gestion. (46:21) L'alignement organisationnel. (48:51) Mobilisation et performance. (54:04) La gestion des entraîneurs professionnels. (56:38) Question : Olivier, si tu pouvais retourner en arrière et donner un conseil à toi-même, quand tu avais 22 ans, ça serait quoi? (1:03:08) Question : Félix, quel livre est-ce que tu as lu, et que tu recommandes le plus en ce moment? (1:04:46) Question : Olivier, qu'est-ce qui va devenir un avantage compétitif dans le monde dans 10 ans? (1:05:51) Question : Félix, si tu pouvais mettre une citation sur un jumbotron dans un aréna ou un stade, ça serait laquelle et qu'est-ce que tu aimerais que les gens comprennent? (1:07:14) Mot de la fin de Félix Bélanger et Olivier Doucet. (1:09:39) PERSONNES ET ORGANISATIONS MENTIONNÉES Olivier Doucet Olivier Doucet | Professor | HEC Montréal Félix Bélanger (27) Félix Bélanger, M. Sc. | LinkedIn Chloé Fortin-Bergeron (30) Chloé Fortin-Bergeron, Ph. D., CRHA | LinkedIn Philadelphia Eagles Philadelphia Eagles Aaron Rodgers Aaron Rodgers Stats, News, Bio | ESPN Martin St. Louis Martin St. Louis - Wikipedia Deion Sanders Deion Sanders - Family, Stats & Facts - Biography Katrien Fransen ‪Katrien Fransen - ‪Google Scholar Hockey Québec | Hockey Québec Alexanne Picard Alexanne Picard - Elite Prospects Michael Lombardi Michael Lombardi (American football) - Wikipedia Kliff Kingsbury Kliff Kingsbury - Wikipedia Claude Julien Claude Julien (ice hockey) - Wikipedia Eric Brunelle Eric Brunelle | Professor | HEC Montréal «The No Asshole Rule» The No Asshole Rule: Building a Civilized Workplace and Surviving One That Isn't: Sutton PhD, Robert I., Sutton PhD, Robert I.: 9781600245855: Amazon.com: Books

Durant cet épisode, je cherche à comprendre la dynamique des équipes et le leadership avec Olivier Doucet, Ph. D., et Félix Bélanger, M. Sc. À propos de nos invités: Olivier Doucet: Olivier Doucet (MBA, Ph.D., CRHA) est professeur titulaire et directeur associé au Pôle sports à HEC Montréal. Il enseigne la gestion de la performance et des talents des employés dans divers programmes. À travers ses recherches, il s'intéresse à l'efficacité des saines pratiques de gestion de la performance, les compétences managériales des gestionnaires et la mobilisation des employés. Il aborde ces thématiques en regard de leur dynamique dans les relations gestionnaire-employé, coach-athlète, ainsi que dans les équipes de travail et sportives. Il a formé des centaines de gestionnaires dans différents pays et il accompagné plusieurs entreprises dans la mise en place de pratiques novatrices de gestion de performance. Il est auteur de plus de 35 articles scientifiques, ouvrages et chapitres de livres. Pour rejoindre Olivier: olivier.doucet@hec.ca Félix Bélanger: Diplômé de l'Université du Québec à Trois-Rivières (UQTR), Félix Bélanger se spécialise dans les dynamiques d'équipes sportives et en sciences de la gestion; sa maîtrise porte d'ailleurs sur les formes collectives de leadership dans les équipes sportives. Comme entraîneur, Félix cumule plusieurs années d'expériences auprès de la franchise des Estacades de la Mauricie de la LHEQ. Il est aujourd'hui entraîneur adjoint pour les Dragons du Collège Laflèche, au niveau collégial D1 du RSEQ. Détenteur de la formation HP1 depuis 2014, Félix Bélanger travaille aussi avec le Pôle Sports du HEC Montréal afin d'améliorer la formation en matière de gestion des équipes pour les entraîneur(e)s de hockey au Québec. Au sein de la Fédération, il a par ailleurs présenté diverses conférences sur le leadership. Pour rejoindre Félix: felix.belanger1@uqtr.ca   Suivez Coach Frank sur TWITTER: https://twitter.com/coachfrankphd Pour rejoindre la communauté: info@bettersport.ca ABONNEZ-VOUS à l'infolettre: https://drcoachfrank.com/contact/ NOTES D'ÉMISSION Introduction de Olivier Doucet et Félix Bélanger et qu'est-ce qu'ils veulent ressortir et soutenir du podcast. (0:05) Une bonne forme de leadership et le «followership ». (6:53) Le leadership est processuel. (9:15) Collaboration et le projet du leadership partagé. (10:40) C'est quoi les ramifications et conclusions qui sortent du leadership partagé? (15:04) Élargir le leadership. (21:51) Citation : « Il faut que tu emmènes ta game dans la game ». (24 :28) Un coach qui a beaucoup de joueurs qui prennent l'autonomie : reconnaître les forces et les faiblesses. (26:19) Le leadership partagé dans le sport. (31:08) Les catégorisations. (34:15) Collecte de données dans le projet avec Hockey Québec. (37:04) Qu'est ce qu'on devrait voir comme résultat en essayant les choses mentionnés dans les données? (40:40) Comment éduquer les jeunes sur le leadership. (44:15) Comment faire le parallèle entre la gestion. (46:21) L'alignement organisationnel. (48:51) Mobilisation et performance. (54:04) La gestion des entraîneurs professionnels. (56:38) Question : Olivier, si tu pouvais retourner en arrière et donner un conseil à toi-même, quand tu avais 22 ans, ça serait quoi? (1:03:08) Question : Félix, quel livre est-ce que tu as lu, et que tu recommandes le plus en ce moment? (1:04:46) Question : Olivier, qu'est-ce qui va devenir un avantage compétitif dans le monde dans 10 ans? (1:05:51) Question : Félix, si tu pouvais mettre une citation sur un jumbotron dans un aréna ou un stade, ça serait laquelle et qu'est-ce que tu aimerais que les gens comprennent? (1:07:14) Mot de la fin de Félix Bélanger et Olivier Doucet. (1:09:39) PERSONNES ET ORGANISATIONS MENTIONNÉES Olivier Doucet Olivier Doucet | Professor | HEC Montréal Félix Bélanger (27) Félix Bélanger, M. Sc. | LinkedIn Chloé Fortin-Bergeron (30) Chloé Fortin-Bergeron, Ph. D., CRHA | LinkedIn Philadelphia Eagles Philadelphia Eagles Aaron Rodgers Aaron Rodgers Stats, News, Bio | ESPN Martin St. Louis Martin St. Louis - Wikipedia Deion Sanders Deion Sanders - Family, Stats & Facts - Biography Katrien Fransen ‪Katrien Fransen - ‪Google Scholar Hockey Québec | Hockey Québec Alexanne Picard Alexanne Picard - Elite Prospects Michael Lombardi Michael Lombardi (American football) - Wikipedia Kliff Kingsbury Kliff Kingsbury - Wikipedia Claude Julien Claude Julien (ice hockey) - Wikipedia Eric Brunelle Eric Brunelle | Professor | HEC Montréal «The No Asshole Rule» The No Asshole Rule: Building a Civilized Workplace and Surviving One That Isn't: Sutton PhD, Robert I., Sutton PhD, Robert I.: 9781600245855: Amazon.com: Books

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.24.517673v1?rss=1 Authors: Stylianakis, E., Festenstein, R., Vannier, J.-B. Abstract: TElomeric Repeat-containing RNA are long non-coding RNAs generated from the telomeres. TERRAs are essential for the establishment of heterochromatin marks at telomeres, which serve for the binding of Heterochromatin Protein 1 (HP1), a protein family of epigenetic modifiers involved with chromatin compaction and gene silencing. While HP1{gamma} is enriched on gene bodies of actively transcribed human and mouse genes, it is unclear if its transcriptional role is important for HP1{gamma} function in telomere cohesion and telomere maintenance. We aimed to study the effect of mouse HP1{gamma} on the transcription of telomere factors and molecules that can affect telomere maintenance. We investigated the telomere function of HP1{gamma} by using deficient mouse embryonic fibroblasts (MEFs) deriving from 13.5 embryonic day embryos compared to their litter mate controls. We used gene expression analysis of HP1{gamma} deficient MEFs and validated the molecular and mechanistic consequences of HP1{gamma} loss by telomere FISH, immunofluorescence, RT-qPCR and DNA-RNA Immunoprecipitation (DRIP). Loss of HP1{gamma} in primary MEFs leads to a downregulation of various telomere and telomere-accessory transcripts, including shelterin protein TRF1. Its downregulation is associated with increased telomere replication stress and DNA damage ({gamma}H2AX), effects more profound in females. We suggest that the source for the impaired telomere maintenance is a consequence of increased telomeric DNA-RNA hybrids and TERRAs arising at and from mouse chromosomes 18 and X. Our results suggest an important transcriptional control by mouse HP1{gamma} of various telomere factors including TRF1 protein and TERRAs that has profound consequences on telomere stability, with a potential sexually dimorphic nature. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Xiaomi anunció sus nuevos teléfonos insignia, el 12T y el 12T Pro. Ambos cuentan con pantalla OLED de 6.67 pulgadas a 120 Hz. El Pro cuenta con el Snapdragon 8 Plus Gen 1 de Qualcomm mientras que el 12T usa el MediaTek Dimensity 8100 Ultra. En el terreno de la óptica, el modelo Pro cuenta con un sensor HP1 de 200 megapíxeles de Samsung para la cámara principal, mientras que el 12T llega a los 108 megapíxeles. Se lanzarán en Europa el 13 de octubre con un precio de 599 euros para el 12T y de 749 euros para el 12T Pro.Para esta y más noticias escucha todos los días el podcast de Noticias de Tecnología Express, disponible en Apple Podcasts, Spotify, Acast, y en cualquier lugar en donde se escuchen podcasts. Disponible en Spotifyhttps://open.spotify.com/show/2BHTUlynDLqEE2UhdIYfMaen Apple Podcastshttps://podcasts.apple.com/us/podcast/noticias-de-tecnolog%C3%ADa-express/id1553334024

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.08.29.505641v1?rss=1 Authors: Newman, A. G., Sharif, J., Bessa, P., Zaqout, S., Brown, J., Nakayama, M., Mueller, S., Böhm-Sturm, P., Ohara, O., Koseki, H., Singh, P., Tarabykin, V. Abstract: In aging cells and animal models of premature aging, heterochromatin loss coincides with the transcriptional activation of normally silenced endogenous retroviruses (ERVs). Here we show that loss of heterochromatin maintenance and de-repression of ERVs results in neurodegeneration via the Complement cascade in an age dependent manner. We discovered differential contributions of HP1 proteins to ERV silencing where HP1{gamma} is necessary and sufficient for H4K20me3 deposition and HP1{beta} deficiency is detrimental to DNA maintenance methylation. Progressive ERV de-repression in HP1{beta}/{gamma} DKO mice was followed by stimulation of the integrated stress response, the induction of Complement 3+ reactive astrocytes and increased infiltration and activation of microglia. This chronic inflammatory state coincided with age-dependent reductions in dendrite complexity and cognition. Our results demonstrate the importance of preventing loss of epigenetic maintenance, as this will be the only way postmitotic neuronal genomes can be protected and/or renewed. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

HP1 – What is Prayer? – The Heart of Prayer with Fr. Éamonn Bourke Fr. Éamonn Bourke and Kris McGregor discuss the why, how, and what of “prayer”?  In this episode, they explore the nature of prayer and responding to the call of relationship with God. Here is an excerpt from their conversation: Fr. Éamonn ... Read more The post HP1 – What is Prayer? – The Heart of Prayer with Fr. Éamonn Bourke – Discerning Hearts Podcast appeared first on Discerning Hearts Catholic Podcasts.

Porque se te descarga tan rápido tu smartphone Android, ademas; Jack Dorsey deja la junta directiva de Twitter 16 años después de haber fundado la compañía; Inversores de Twitter demandan a Elon Musk por acusaciones de manipulación de acciones; Broadcom está comprando VMware en un mega acuerdo de $ 61 mil millones y mucho mas. Los temas del día: Instagram está caído, los usuarios reportan problemas para iniciar sesión https://twitter.com/JOstrovska/status/1529902445593251845? Gboard pronto puede agregar un teclado dividido para tabletas y plegables https://www.xda-developers.com/gboard-split-keyboard-coming-soon/? Broadcom está comprando VMware en un mega acuerdo de $ 61 mil millones https://www.engadget.com/broadcom-buys-vmware-125814712.html? Sony planea aumentar su producción de PlayStation 5 para satisfacer la alta demanda https://www.sony.com/en/SonyInfo/IR/library/presen/irday/pdf/2022/GNS_E.pdf Inversores de Twitter demandan a Elon Musk por acusaciones de manipulación de acciones https://www.engadget.com/twitter-investors-elon-musk-stock-manipulation-lawsuit-190557864.html? Samsung flexiona su sensor HP1 de 200MP imprimiendo una cartelera de gatos https://youtu.be/7AS2XQ_VbA4 Jack Dorsey deja la junta directiva de Twitter 16 años después de haber fundado la compañía https://actualidad.rt.com/actualidad/430915-twitter-jack-dorsey-renuncia-directorio? APOYANOS DESDE PAYPAL https://www.paypal.me/arielmcorg APOYANOS DESDE PATREON https://www.patreon.com/radiogeek APOYANOS DESDE CAFECITO https://cafecito.app/radiogeek Podes seguirme desde Twitter @arielmcorg (www.twitter.com/arielmcorg) También desde Instagram @arielmcorg (www.instagram.com/arielmcorg) Sumate al canal de Telegram #Radiogeekpodcast (http://telegram.me/Radiogeekpodcast)

Nitwit! Blubber! Oddment! Tweak!Happy (early) Christmas to our wonderful listeners! Grab your wands and mount your brooms - it's time for Season Two's first watch-along.If you've never participated in a watch-along before, here's what to do:Find a copy of the film (DVD, streaming, digital download -- they all work. But the ladies don't condone illegal activities, even for the movies they hate!);Turn on the podcast;Press 'Play' when the ladies give the go-ahead;Enjoy!Like what you hear? Support the podcast through Buy Me A Coffee!Support the show

In this episode of the Epigenetics Podcast, we caught up with Serena Sanulli from Stanford University to talk about her work on Heterochromatin Protein 1 (HP1), the structure of chromatin on the atomic-scale and the meso-scale, and phase separation. The Laboratory of Serena Sanulli is interested in finding connections between changes that happen on the nucleosomal level and the resulting impact on chromatin conformation on the meso-scale. They combine methods like NMR and Hydrogen-Deuterium Exchange-MS with Cell Biology and Genetics. This enables them to dissect how cells use the diverse biophysical properties of chromatin to regulate gene expression across length and time scales. A second focus of the lab is HP1, which interacts with the nucleosome and changes its conformation, enabling the compaction of the genome into heterochromatin, effectively silencing genes in that region. A high concentration of HP1 leads to the phenomenon of phase separation in the nucleus, which the Sanulli lab is now investigating.   References Sanulli, S., Justin, N., Teissandier, A., Ancelin, K., Portoso, M., Caron, M., Michaud, A., Lombard, B., da Rocha, S. T., Offer, J., Loew, D., Servant, N., Wassef, M., Burlina, F., Gamblin, S. J., Heard, E., & Margueron, R. (2015). Jarid2 Methylation via the PRC2 Complex Regulates H3K27me3 Deposition during Cell Differentiation. Molecular Cell, 57(5), 769–783. https://doi.org/10.1016/j.molcel.2014.12.020 Sanulli, S., Trnka, M. J., Dharmarajan, V., Tibble, R. W., Pascal, B. D., Burlingame, A. L., Griffin, P. R., Gross, J. D., & Narlikar, G. J. (2019). HP1 reshapes nucleosome core to promote phase separation of heterochromatin. Nature, 575(7782), 390–394. https://doi.org/10.1038/s41586-019-1669-2 Sanulli, S., & Narlikar, G. J. (2021). Generation and Biochemical Characterization of Phase‐Separated Droplets Formed by Nucleic Acid Binding Proteins: Using HP1 as a Model System. Current Protocols, 1(5). https://doi.org/10.1002/cpz1.109   Related Episodes Transcription and Polycomb in Inheritance and Disease (Danny Reinberg) Heterochromatin and Phase Separation (Gary Karpen)   Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com

Harry Potter und die Kammer des Schreckens - Kapitel 7 Die unheimliche Stimme - Radio Ravenclaw

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.30.362772v1?rss=1 Authors: Keenen, M. M., Brown, D., Brennan, L. D., Renger, R., Khoo, H., Carlson, C. R., Huang, B., Grill, S. W., Narlikar, G. J., Redding, S. Abstract: In mammals HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1, HP1{beta}, and HP1{gamma}, display rapid on-off dynamics. Here we investigate whether phase-separation by HP1 proteins can explain these biological observations. Using bulk and single-molecule methods, we show that, within phase-separated HP1-DNA condensates, HP1 acts as a dynamic liquid, while compacted DNA molecules are constrained in local territories. These condensates are resistant to large forces yet can be readily dissolved by HP1{beta}. Finally, we find that differences in each HP1 paralog's DNA compaction and phase-separation properties arise from their respective disordered regions. Our findings suggest a generalizable model for genome organization in which a pool of weakly bound proteins collectively capitalize on the polymer properties of DNA to produce self-organizing domains that are simultaneously resistant to large forces at the mesoscale and susceptible to competition at the molecular scale. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.09.331900v1?rss=1 Authors: Strom, A. R., Biggs, R. J., Banigan, E. J., Wang, X., Chiu, K., Herman, C., Collado, J., Yue, F., Ritland Politz, J. C., Tait, L. J., Scalzo, D., Telling, A., Groudine, M., Brangwynne, C. P., Marko, J., Stephens, A. D. Abstract: Chromatin, which consists of DNA and associated proteins, contains genetic information and is a mechanical component of the nucleus. Heterochromatic histone methylation contributes to nucleus and chromosome stiffness, but the contribution of heterochromatin protein HP1 (CBX5) is unknown. Here we used a novel HP1 auxin-inducible degron human cell line to rapidly degrade HP1. Degradation did not alter transcription, chromatin compaction, or histone methylation, but did decrease chromatin stiffness. Single-nucleus micromanipulation reveals that HP1 is essential to chromatin-based mechanics and maintains nuclear morphology, separate from histone methylation. Further experiments with dimerization-deficient HP1I165E indicate that chromatin crosslinking via HP1 dimerization is critical, while polymer simulations demonstrate the importance of chromatin-chromatin crosslinkers in mechanics. In mitotic chromosomes, HP1 similarly bolsters stiffness while aiding in mitotic alignment and faithful segregation. HP1 is therefore a critical chromatin-crosslinking protein that supports cellular functions by providing mechanical strength to chromosomes and the nucleus throughout the cell cycle. Copy rights belong to original authors. Visit the link for more info

In this episode of the Epigenetics Podcast, we caught up with Geneviève Almouzni, Ph.D., Research Director at the CNRS at Institut Curie in Paris, to talk about her work on the regulation of chromatin organization by histone chaperones. Geneviève Almouzni got her Ph.D. from Université Pierre-et-Marie-Curie in 1988 under the supervision of Marcel Méchali. She then moved to the United States to work as a postdoc in the National Institutes of Health in the laboratory of Professor Alan Wolffe. In 1994, she returned to Paris and became a Junior Group Leader at Institut Curie and became a Group Leader there in 2000. In 2013, she took over the direction of research at the Institut Curie and became the third woman to hold this position, after Marie Curie and Irène Joliot-Curie. Geneviève Almouzni’s research focuses on the assembly of chromatin and the identification of histone chaperones. Histone chaperones are necessary for the establishment and maintenance of chromatin, as they help to assemble the nucleosomes out of the core histones and DNA. This occurs both when the polymerase transcribes through a nucleosome and after DNA replication and repair. The Almouzni group has identified and characterized multiple histone chaperones, including CAF-1, HirA, and HJURP. Furthermore, they investigated how post-translational modifications on soluble histones influence the final epigenetic state of the nucleosome and the reassembly of chromatin after DNA replication. In the last couple of years, the group has focused on the unraveling the link between the structure of chromatin at centromeres and cancer. In this interview, we discuss the focus of the Almouzni lab on histone chaperones, how the lab was able to identify its first one with CAF-1, how histone PTMs on soluble histones influence the deposition on the DNA, and how the chromatin on centromeres is involved in cancer.   References   Dominique Ray-Gallet, Jean-Pierre Quivy, … Geneviève Almouzni (2002) HIRA Is Critical for a Nucleosome Assembly Pathway Independent of DNA Synthesis (Molecular Cell) DOI: 10.1016/S1097-2765(02)00526-9 Pierre-Henri L. Gaillard, Emmanuelle M.-D. Martini, … Geneviève Almouzni (1996) Chromatin Assembly Coupled to DNA Repair: A New Role for Chromatin Assembly Factor I (Cell) DOI: 10.1016/S0092-8674(00)80164-6 Jean-Pierre Quivy, Danièle Roche, … Geneviève Almouzni (2004) A CAF-1 dependent pool of HP1 during heterochromatin duplication (The EMBO Journal) DOI: 10.1038/sj.emboj.7600362   Contact   Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on Linked-In Active Motif on Facebook eMail: podcast@activemotif.com  

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.19.210518v1?rss=1 Authors: Singh, P. B., Belyakin, S. N., Laktionov, P. P. Abstract: The hallmarks of constitutive heterochromatin, HP1 and H3K9me2/3, assemble heterochromatin-like domains/complexes outside canonical constitutively heterochromatic territories where they regulate chromatin-templated processes. Domains are more than 100kb in size; complexes less than 100kb. They are present in the genomes of organisms ranging from fission yeast to man, with an expansion in size and number in mammals. Some of the likely functions of the domains/complexes include silencing of the donor mating type region in fission yeast, regulation of mammalian imprinted genes and the phylotypic progression during vertebrate development. Far cis- and trans-contacts between micro-phase separated domains/complexes in mammalian nuclei contribute to the emergence of epigenetic compartmental domains (ECDs) detected in Hi-C maps. We speculate that a thermodynamic description of micro-phase separation of heterochromatin-like domains/complexes will require a gestalt shift away from the monomer as the "unit of incompatibility", where it is the choice of monomer that determines the sign and magnitude of the Flory-Huggins parameter, {chi}. Instead, a more dynamic structure, the oligo-nucleosomal "clutch", consisting of between 2 to 10 nucleosomes is both the long sought-after secondary structure of chromatin and its unit of incompatibility. Based on this assumption we present a simple theoretical framework that enables an estimation of {chi} for domains/complexes flanked by euchromatin and thereby an indication of their tendency to phase separate. The degree of phase separation is specified by {chi}N, where N is the number of "clutches" in a domain/complex. Our approach may provide an additional tool for understanding the biophysics of the 3D genome. Copy rights belong to original authors. Visit the link for more info

Harry Potter und der Stein der Weisen - Kapitel 15: Der verbotene Wald Mandy

Wer ist Nicolas Flamel? Warum hat Hagrid so merkwürdig reagiert und was hat es mit dem Päckchen aus Verlies 713 auf sich? Und vor allem: Wo hat Harry diesen Namen schon mal gehört? Ach ja, und Snape ist Quidditch Schiedsrichter. Yay! The Irrelevants auf Youtube:

Was ist dein größter Wunsch? Die ewige Liebe? Extrem viel Geld? Der Tod? Der Spiegel Nerhegeb zeigt dem Menschen, der hineinsieht eben genau das. Was dies für Harry, Ron und Dumbledore ist oder sein könnte diskutieren wir in dieser Ausgabe von Radio Ravenclaw Mandy

Harry duelliert sich direkt im ersten Buch? Wir waren überrascht und das *SPOILER* sterben würde. Wer hätte das gedacht ? Mandy

Professor Snape ist einer der spannendsten Charaktere der Harry Potter Bücher. Tiefgründig wirkt er jedoch auf dem ersten Blick nicht, mehr so wie ein überböser Mathematiklehrer aus mittelmäßigen Highschool Dramen. Ob da mehr hintersteckt untersuchen wir in Kapitel 8: der Meister der Zaubertränke! Mandy

In welches Haus gehörst du und wofür steht das? In der Welt von Harry Potter müssen sich die Schüler keine Gedanken darum machen, denn es gibt ja den Sprechenden Hut! Einmal aufgesetzt entscheidet er wer wohin kommt und somit auch irgendwie die Zukunft des jungen Zauberers oder Mandy

Aus der Winkelgasse zum berühmtesten Gleis der Zaubererwelt: Gleis neundreiviertel! Harry trifft auf seine zukünftigen Mitschüler, u. a. die zickige Hermine und der nervöse Ron. Schicksalhafte Begegnungen und "Wir hätten gern alles!" in Kapitel 6 von Radio Ravenclaw. Mandy

The Infinity War trailer is finally here! And Drew and Houston have a whole lot of...uh...rambles to go on. It's a jolly old time. Theories. Speculation. Fun. Thanks for listening. Follow Drew on Twitter at @nerd_stream7 and Houston at @blockbustedpod! Email us at blockbustedpodcast@yahoo.com. If you enjoy Blockbusted or HP1 and you'd like to support the show, be sure to visit the HP1 Patreon right here: https://www.patreon.com/user?u=1017531

What 3-5 movies should everyone see in their lifetime? • 6/30 Sign off • 4 Top Movies I'd Recommend • Response to Gabby's call-in • Movies to see before you die? • Response to HP1's call-in • Five Movies To See Before You Die • Response to Chance

The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. These proteins contain two related domains known as the chromo- and the chromoshadow-domain. The chromo- domain binds histone H3 tails methylated on lysine 9. However, in vivo and in vitro experiments have shown that the affinity of HP1 proteins to native methylated chromatin is relatively poor and that the opening of chromatin occurring during DNA replication facilitates their binding to nucleosomes. These observations prompted us to investigate whether HP1 proteins have additional histone binding activities, envisioning also affinity for regions potentially occluded by the nucleosome structure. We find that the chromoshadow-domain interacts with histone H3 in a region located partially inside the nucleosomal barrel at the entry/exit point of the nucleosome. Interestingly, this region is also contacted by the catalytic subunits of the human SWI/SNF complex. In vitro, efficient SWI/SNF remodeling requires this contact and is inhibited in the presence of HP1 proteins. The antagonism between SWI/SNF and HP1 proteins is also observed in vivo on a series of interferon-regulated genes. Finally, we show that SWI/SNF activity favors loading of HP1 proteins to chromatin both in vivo and in vitro. Altogether, our data suggest that HP1 chromoshadow-domains can benefit from the opening of nucleosomal structures to bind chromatin and that HP1 proteins use this property to detect and arrest unwanted chromatin remodeling.

HP1 is a major component of chromatin and regulates gene expression through its binding to methylated histone H3. Most eukaryotes express at least three isoforms of HP1 with similar domain architecture. However, despite the common specificity for methylated histone H3, the three HP1 isoforms bind to different regions of the genome. Most of the studies so far focused on the HP1a isoform and its role in transcriptional regulation. As HP1a requires additional factors to bind methylated chromatin in vitro, we wondered whether another isoform might also require additional targeting factors. Indeed, we found that HP1c interacts with the DNA binding factors Woc and Row and requires Woc to become targeted to chromatin in vivo. Moreover, we show that the interaction between HP1c and Woc constitutes a transcriptional feedback loop that operates to balance the concentration of HP1c within the cell. This regulation may prevent HP1c from binding to methylated heterochromatin.

In most eukaryotes the histone methyltransferases SU(VAR)3-9, G9a and their orthologues play major roles in transcriptional regulation. Histone H3 lysine 9 methylation is associated to transcriptional silencing in vivo. SU(VAR)3-9 is the main H3K9 HMTase in Drosophila heterochromatin whereas G9a was found to be an euchromatic H3K9 methyltransferase in mammalian cells. In this work SU(VAR)3-9 and a new HMTase homologous to G9a were characterized in vitro. A detailed analysis of the reaction products shows that recombinant SU(VAR)3-9 adds three methylgroups to full-length H3 and only two methylgroups to an H3-tail peptide. The transfer of two methylgroups to an unmethylated H3-tail peptide is achieved in a nonprocessive manner. The full-length enzyme elutes with an apparent molecular weight of 160 kDa from a gel filtration column, which indicates the formation of a dimer. The N-terminus was shown to be required for this dimerisation and to retrieve full activity in vitro. We show that the interaction occurs by domain swapping of two motifs within the N-terminus. The fact that the N-terminus is responsible for a concentration dependent dimerisation of SU(VAR)3-9 may indicate a role for this domain in the dosage-dependent effect on position effect variegation. Drosophila G9a adds three methyl groups to unmethylated H3 in vitro as has been described for mouse G9a. In vitro, a N-terminal truncation of dG9a adds three methylgroups toward H3K9 and K27, with a preference for K9. Surprisingly, dG9a also methylates H4 with specificity for K8, K12 or K16. In vivo, dG9a is present in complexes with a molecular mass of 440-670 kDa and we show that it specifically interacts with the histone deacetylase Rpd3. HP1a is predominantly associated with centromeric heterochromatin in Drosophila. Supporting the histone code hypothesis, the chromo domain of HP1 recognises and binds H3K9 methylated peptides. Here we show the mechanism for binding to H3K9Me chromatin by recombinant Drosophila HP1a. HP1a requires a bimodal interaction of the chromo domain with H3K9Me and a simultaneous interaction of the chromo shadow domain with auxiliary factors (SU(VAR)3-9 and ACF) for stable association with H3K9Me chromatin. The two HP1 paralogs HP1a and HP1c bind to distinct chromatin structures and we identify distinct interaction partners for these two proteins.

In der vorliegenden Arbeit wurden die beiden Histon-Methyltransferasen Su(var)3-9 und E(Z) aus Drosophila melanogaster charakterisiert. Die Histonmethylierung als Modifikation war schon länger bekannt gewesen, bis zum Jahr 2000 war jedoch vor allem die Acetylierung etwas genauer untersucht worden. Su(var)3-9 war die einzige bekannte Histon-Lysin-Methyltransferase, als diese Arbeit begonnen wurde. Zur Charakterisierung wurde das myc-getagte Enzym aus Drosophila-Kernextrakt durch Affinitätschromatographie aufgereinigt und zunächst die Substratspezifität festgestellt. Wie das humane Enzym Suv39H1 methyliert es ebenfalls spezifisch H3-K9 (Lysin 9 im Histon H3). Das aus den Kernextrakten aufgereinigte Enzym besitzt aber auch die Fähigkeit, ein an H3-K9 präacetyliertes Substrat zu methylieren. Die Vermutung, dass Su(var)3-9 mit einer Histondeacetylase assoziiert ist, konnte durch Verwendung von TSA als HDAC-Inhibitor bestätigt werden. Es stellte sich heraus, dass HDAC1 (Rpd3) mit Su(var)3-9 assoziiert ist. Um das Enzym besser untersuchen zu können, wurde es als Volllängenprotein und als Deletionsmutante in E. coli exprimiert. Die Aufreinigung des rekombinanten Enzyms sowie seine Lagerbedingungen wurden optimiert. Das Volllängenprotein Su(var)3-9 liegt – wie durch Gelfiltration festgestellt - als Dimer vor, die Interaktion mit sich selbst ist über den N-Terminus vermittelt. Su(var)3-9 bindet an sein eigenes, bereits methyliertes Substrat. Dies wurde an Peptiden untersucht, die den ersten 20 Aminosäuren des Histons H3 entsprechen, und entweder an Lysin 9 dimethyliert oder unmodifiziert waren. Die Interaktion mit dem methylierten Substrat ist auf die Chromodomäne von Su(var)3-9 zurückzuführen, ist jedoch schwächer als die Wechselwirkung von HP1 mit methyliertem H3-K9. Des weiteren wurde eine Drosophila-Zelllinie stabil mit Su(var)3-9 transfiziert. Das überexprimierte Protein ist jedoch nur schwach aktiv. Die Tatsachen, dass Su(var)3-9 mit HDAC1 interagiert sowie mit seinem eigenen Substrat assoziiert, ermöglichen die Aufstellung von Hypothesen über die bis jetzt kaum erhellte Ausbreitung von Heterochromatin in euchromatische Bereiche. Durch die Wechselwirkung mit der Deacetylase könnte Su(var)3-9 auch in aktiv transkribierte Bereiche vordringen und diese methylieren. Die Acetylierung, Zeichen für aktive Transkription, würde durch die Methylierung ersetzt werden. Die Interaktion mit seinem umgesetzten Substrat könnte verhindern, dass das Enzym sich nach der Reaktion entfernt, vielmehr könnte Su(var)3-9 entlang eines DNA-Stranges sukzessive alle Nukleosomen methylieren. Die darauffolgende Bindung von HP1 an methyliertes H3-K9 könnte den heterochromatischen Charakter des Chromatins verstärken und für längere Zeit festlegen. Aus Drosophila-Kernextrakten gelang es weiterhin, den E(Z)/ESC-Komplex über Säulenchromatographie aufzureinigen. Dieser enthält neben E(Z), ESC, p55 und Rpd3 auch Su(z)12. E(Z), ESC und Su(z)12 gehören der Polycomb-Gruppe an. Deren Funktion ist die dauerhafte Repression der homöotischen Gene. Sie spielen daher eine wichtige Rolle im „Zellgedächtnis“ während der frühen Entwicklung von Drosophila. Es konnte gezeigt werden, dass der E(Z)/ESC-Komplex Lysin 9 sowie Lysin 27 im Histon H3 methyliert. Außerdem wurde in vitro ein Teilkomplex aus rekombinantem E(Z), p55 und ESC rekonstituiert, der das Histon H3 methylieren kann. Ein Teilkomplex, der E(Z) mit mutierter SET-Domäne enthält, ist nicht in der Lage, H3 zu methylieren. Die Vorhersage, dass E(Z) aufgrund seiner SET-Domäne eine Methyltransferase sein müsse, konnte durch vorliegende Untersuchungen bestätigt werden. Polycomb ist ein weiteres Protein aus der Polycomb-Gruppe. In dieser Arbeit konnte gezeigt werden, dass dieses Protein spezifisch an das Histon H3 bindet, das an K27 trimethyliert ist. Polycomb besitzt wie HP1 eine Chromodomäne. Aus den vorliegenden Daten kann folgendes Modell aufgestellt werden: Nach der Methylierung von H3-K9 sowie H3-K27 durch den E(Z)/ESC-Komplex in homöotischen Genen, die schon abgeschaltet sind und weiterhin reprimiert werden müssen, bindet Polycomb an dieses Methylierungsmuster. Polycomb befindet sich in einem großen Komplex mit weiteren Polycomb-Gruppen-Proteinen. Die Bindung dieses Komplexes an Chromatin könnte ein denkbarer Mechanismus sein, wie die dauerhafte Repression der homöotischen Gene vermittelt wird. Um den E(Z)/ESC-Komplex genauer untersuchen zu können, wurden Viren für das Baculosystem hergestellt, so dass eine Einzel- oder auch Coexpression der Proteine möglich ist. Die Aktivität von E(Z), das im Baculosystem exprimiert wurde, ist nicht besonders hoch. Es bindet unter den in dieser Arbeit verwendeten Bedingungen weder an DNA, noch an Histone noch an H3-Peptide, die methyliert sind. Innerhalb des E(Z)/ESC-Komplexes bindet E(Z) an p55, Rpd3, ESC sowie Su(z)12. Su(z)12 interagiert mit p55, Rpd3 und E(Z). Die weiteren Interaktionen werden am besten durch eine bildliche Darstellung (siehe Abb. 86) vermittelt. In einem Luciferase-Assay wurde eine repressive Wirkung von E(Z) festgestellt. Dieses Experiment bedarf allerdings eines aktivierten Systems. Ferner muss durch Mutationsanalysen sichergestellt werden, dass die repressive Wirkung auf die Methyltransferase-Aktivität von E(Z) zurückzuführen ist. Kürzlich wurde entdeckt, dass E(Z) sowie Su(z)12 in verschiedenen Tumoren überexprimiert sind. Noch ist weder deren Funktion in den Tumorzellen klar, noch weiss man, ob die Überexpression der Grund oder eine Folge der Tumorbildung ist, noch kennt man alle Zielgene, die durch eine Überexpression von E(Z) und Su(z)12 beeinflusst werden. In nächster Zeit sind hier Einsichten in die Wirkungsweise von E(Z), Su(z)12 und anderen Polycomb-Gruppen-Proteinen zu erwarten.