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Epigenetics Podcast

By: Active Motif
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  • Discover the stories behind the science!
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Episodes
  • Comparing CUT&Tag to ENCODE ChIP-Seq in Alzheimer's Disease Samples (Sarah Marzi)

    Comparing CUT&Tag to ENCODE ChIP-Seq in Alzheimer's Disease Samples (Sarah Marzi)
    Apr 18 2024
    In this episode of the Epigenetics Podcast, we talked with Sarah Marzi from the UK Dementia Research Institute at Imperial College London about her work on epigenetic changes in Alzheimer's Disease, and comparing CUT&Tag to ENCODE ChIP-Seq using limited cell samples. The interview discusses Sarah Marzi's work on ChIP-Seq experiments and their significance in understanding Alzheimer's disease from an epigenetic perspective. The discussion touches on the widespread dysregulation and changes in acetylation, particularly in genes associated with Alzheimer's risk, providing insights into potential links between epigenetic insults and disease onset. Moving on to the technical aspects of the study, the interview examines the strategic use of CUT&Tag. It explores the challenges and optimizations involved in accurately profiling limited cell samples. The dialogue also compares CUT&Tag to ENCODE ChIP-Seq, highlighting the complexities of peak calling and data interpretation across different methodologies. References Kumsta, R., Marzi, S., Viana, J. et al. Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1. Transl Psychiatry 6, e830 (2016). https://doi.org/10.1038/tp.2016.95 Marzi, S. J., Schilder, B. M., Nott, A., Frigerio, C. S., Willaime‐Morawek, S., Bucholc, M., Hanger, D. P., James, C., Lewis, P. A., Lourida, I., Noble, W., Rodriguez‐Algarra, F., Sharif, J., Tsalenchuk, M., Winchester, L. M., Yaman, Ü., Yao, Z., The Deep Dementia Phenotyping (DEMON) Network, Ranson, J. M., & Llewellyn, D. J. (2023). Artificial intelligence for neurodegenerative experimental models. Alzheimer’s & Dementia, 19(12), 5970–5987. https://doi.org/10.1002/alz.13479 Marzi, S. J., Leung, S. K., Ribarska, T., Hannon, E., Smith, A. R., Pishva, E., Poschmann, J., Moore, K., Troakes, C., Al-Sarraj, S., Beck, S., Newman, S., Lunnon, K., Schalkwyk, L. C., & Mill, J. (2018). A histone acetylome-wide association study of Alzheimer’s disease identifies disease-associated H3K27ac differences in the entorhinal cortex. Nature Neuroscience, 21(11), 1618–1627. https://doi.org/10.1038/s41593-018-0253-7 Hu, D., Abbasova, L., Schilder, B. M., Nott, A., Skene, N. G., & Marzi, S. J. (2022). CUT&Tag recovers up to half of ENCODE ChIP-seq peaks in modifications of H3K27 [Preprint]. Genomics. https://doi.org/10.1101/2022.03.30.486382 Related Episodes When is a Peak a Peak? (Claudio Cantù) Development of Integrative Machine Learning Tools for Neurodegenerative Diseases (Enrico Glaab) DNA Methylation Alterations in Neurodegenerative Diseases (Paula Desplats) 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
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    47 mins
  • The Role of Hat1p in Chromatin Assembly (Mark Parthun)

    The Role of Hat1p in Chromatin Assembly (Mark Parthun)
    Apr 4 2024
    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
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    48 mins
  • The Impact of Paternal Diet on Offspring Metabolism (Upasna Sharma)

    The Impact of Paternal Diet on Offspring Metabolism (Upasna Sharma)
    Mar 21 2024
    In this episode of the Epigenetics Podcast, we talked with Upasna Sharma from UC Santa Cruz about her work on a number of interesting projects on H2A.Z and telomeres, the impact of paternal diet on offspring metabolism, and the role of small RNAs in sperm. In this interview Upasna Sharma discusses her work on the study of the paternal diet's impact on offspring metabolism. She reveals the discovery of small non-coding RNAs, particularly tRNA fragments, in mature mammalian sperm that may carry epigenetic information to the next generation. She explains the specific alterations in tRNA fragment levels in response to a low-protein diet and the connections found between tRNA fragments and metabolic status. Dr. Sharma further explains the degradation and stabilization of tRNA fragments in cells and the processes involved in their regulation. She shares their observation of tRNA fragment abundance in epididymal sperm, despite the sperm being transcriptionally silent at that time. This leads to a discussion on the role of the epididymis in the reprogramming of small RNA profiles and the transportation of tRNA fragments through extracellular vesicles. The conversation then shifts towards the potential mechanism of how environmental information could be transmitted to sperm and the observed changes in small RNAs in response to a low-protein diet. Dr. Sharma discusses the manipulation of small RNAs in embryos and mouse embryonic stem cells, revealing their role in regulating specific sets of genes during early development. However, the exact mechanisms that link these early changes to metabolic phenotypes are still being explored. References Sharma, U., Conine, C. C., Shea, J. M., Boskovic, A., Derr, A. G., Bing, X. Y., Belleannee, C., Kucukural, A., Serra, R. W., Sun, F., Song, L., Carone, B. R., Ricci, E. P., Li, X. Z., Fauquier, L., Moore, M. J., Sullivan, R., Mello, C. C., Garber, M., & Rando, O. J. (2016). Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science (New York, N.Y.), 351(6271), 391–396. https://doi.org/10.1126/science.aad6780 Sharma, U., Sun, F., Conine, C. C., Reichholf, B., Kukreja, S., Herzog, V. A., Ameres, S. L., & Rando, O. J. (2018). Small RNAs Are Trafficked from the Epididymis to Developing Mammalian Sperm. Developmental cell, 46(4), 481–494.e6. https://doi.org/10.1016/j.devcel.2018.06.023 Rinaldi, V. D., Donnard, E., Gellatly, K., Rasmussen, M., Kucukural, A., Yukselen, O., Garber, M., Sharma, U., & Rando, O. J. (2020). An atlas of cell types in the mouse epididymis and vas deferens. eLife, 9, e55474. https://doi.org/10.7554/eLife.55474 Related Episodes The Epigenetics of Human Sperm Cells (Sarah Kimmins) Transgenerational Inheritance and Evolution of Epimutations (Peter Sarkies) The Role of Small RNAs in Transgenerational Inheritance in C. elegans (Oded Rechavi) 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
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    37 mins
Biological Sciences
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