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Epigenetics Podcast

Epigenetics Podcast

著者： Active Motif
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 Discover the stories behind the science!Copyright 2020. All rights reserved. 生物科学 科学
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  • The Impact of Chromatin Architecture on Alzheimer's and Parkinson's Disease (Ryan Corces)

    The Impact of Chromatin Architecture on Alzheimer's and Parkinson's Disease (Ryan Corces)
    2025/10/16
    In this episode of the Epigenetics Podcast, we talked with Ryan Corces from the Gladstone Institutes about his work on the impact of chromatin architecture on Alzheimer's and Parkinson's Disease. The discussion begins in discussing he start of Dr. Corces research career and he shares his groundbreaking findings in acute myeloid leukemia (AML), demonstrating how mutations occurring in hematopoietic stem cells lead to the evolution of this disease. He emphasizes the pivotal role of epigenetic modifiers and how these insights steered his focus towards epigenetic research. As the conversation progresses, Dr. Corces covers his transition to a postdoctoral role, emphasizing his collaborative work employing the ATAC-seq technique. He details how refinements to this protocol not only improved data quality but also paved the way for more expansive research within the fields of hematology and cancer genetics. Additionally, he discusses his excitement for developing new computational tools for single-cell analysis, aiming to address the critical challenge of distinguishing between cellular states effectively. The episode also explores the fascinating intersection of Alzheimer’s and Parkinson’s diseases. Dr. Corces explains the rationale for studying both conditions simultaneously, shedding light on the shared and divergent pathological features that emerge in patients. He argues for the importance of understanding mixed pathologies, which reflect the reality for many individuals diagnosed with these neurodegenerative diseases. References Corces, M. R., Trevino, A. E., Hamilton, E. G., Greenside, P. G., Sinnott-Armstrong, N. A., Vesuna, S., Satpathy, A. T., Rubin, A. J., Montine, K. S., Wu, B., Kathiria, A., Cho, S. W., Mumbach, M. R., Carter, A. C., Kasowski, M., Orloff, L. A., Risca, V. I., Kundaje, A., Khavari, P. A., Montine, T. J., … Chang, H. Y. (2017). An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nature methods, 14(10), 959–962. https://doi.org/10.1038/nmeth.4396 Corces, M. R., Granja, J. M., Shams, S., Louie, B. H., Seoane, J. A., Zhou, W., Silva, T. C., Groeneveld, C., Wong, C. K., Cho, S. W., Satpathy, A. T., Mumbach, M. R., Hoadley, K. A., Robertson, A. G., Sheffield, N. C., Felau, I., Castro, M. A. A., Berman, B. P., Staudt, L. M., Zenklusen, J. C., … Chang, H. Y. (2018). The chromatin accessibility landscape of primary human cancers. Science (New York, N.Y.), 362(6413), eaav1898. https://doi.org/10.1126/science.aav1898 Corces, M. R., Trevino, A. E., Hamilton, E. G., Greenside, P. G., Sinnott-Armstrong, N. A., Vesuna, S., Satpathy, A. T., Rubin, A. J., Montine, K. S., Wu, B., Kathiria, A., Cho, S. W., Mumbach, M. R., Carter, A. C., Kasowski, M., Orloff, L. A., Risca, V. I., Kundaje, A., Khavari, P. A., Montine, T. J., … Chang, H. Y. (2017). An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nature methods, 14(10), 959–962. https://doi.org/10.1038/nmeth.4396 Sant, C., Mucke, L., & Corces, M. R. (2025). CHOIR improves significance-based detection of cell types and states from single-cell data. Nature genetics, 57(5), 1309–1319. https://doi.org/10.1038/s41588-025-02148-8 Related Episodes ATAC-Seq, scATAC-Seq and Chromatin Dynamics in Single-Cells (Jason Buenrostro) Multiple challenges of ATAC-Seq, Points to Consider (Yuan Xue) 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
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    46 分
  • RNA-Mediated Epigenetic Regulation (Mo Motamedi)

    RNA-Mediated Epigenetic Regulation (Mo Motamedi)
    2025/10/02
    In this episode of the Epigenetics Podcast, we talked with Mo Motamedi from the Center for Cancer Research at Massachusetts General Hospital about his work on RNA-mediated epigenetic regulation. The Interview starts with Dr. Motamedi sharing his personal journey into the realm of biology, sparked by a familial inclination towards science and a challenge to excel in a field that initially felt daunting. His passion was ignited during a genetics class, as he recognized the quantitative nature of the discipline amidst the evolution of modern techniques like qPCR and high-throughput sequencing. Dr. Motamedi goes on to articulate the importance of understanding the interplay between genetics and broader biological systems, emphasizing that an insightful grasp of evolution is vital for decoding cellular mechanisms. He reflects on his time in a postdoctoral lab under Danesh Moazed, investigating RNA interference (RNAi) and its unexpected nuclear roles, contributing significantly to the understanding of how RNAi is involved in gene silencing via chromatin interaction. As his narrative unfolds, Dr. Motamedi provides deep insights into his own lab's work, which focuses on the establishment and maintenance of epigenetic states and their implications in cancer epigenetics. He discusses groundbreaking discoveries related to RNAi and heterochromatin, detailing experiments that unveil how specific proteins contribute to transcriptional and post-transcriptional gene silencing. A pivotal theme emerges: the complex dynamics of genome evolution and chromatin organization can be reshaped under various biological contexts, including the quiescent state of cells under stress. Moreover, the discussion traverses recent publications from Dr. Motamedi's lab, revealing how they identify long non-coding RNAs that function as silencers at centromeres, an essential mechanism that aids in the establishment of heterochromatin independently of RNAi. His findings advocate for the idea that well-structured genome organization can lead to more efficient gene regulation, which can also be crucial in therapeutic contexts for various cancers. References Motamedi, M. R., Hong, E. J., Li, X., Gerber, S., Denison, C., Gygi, S., & Moazed, D. (2008). HP1 proteins form distinct complexes and mediate heterochromatic gene silencing by nonoverlapping mechanisms. Molecular cell, 32(6), 778–790. https://doi.org/10.1016/j.molcel.2008.10.026 Joh RI, Khanduja JS, Calvo IA, Mistry M, Palmieri CM, Savol AJ, Hoi Sui SJ, Sadreyev RI, Aryee MJ, and Motamedi M. Survival in quiescence requires the euchromatic deployment of Clr4/SUV39H by argonaute-associated small RNAs. † Mol Cell. 2016; 64: 1088-1101. J. S. Khanduja, R. I. Joh, M. M. Perez, J. A. Paulo, C. M. Palmieri, J. Zhang, A. O. D. Gulka, W. Haas, S.P. Gygi, M. Motamedi. RNA quality control factors nucleate Clr4/SUV39H and trigger constitutive heterochromatin assembly. Cell 2024. 187: 3262-3283. *Equal contributions R. I. Joh, M. S. Lawrence, M. J. Aryee, M. Motamedi. Gene clustering drives the transcriptional coherence of disparate biological pathways in eukaryotes. bioRxiv 2023. doi: 10.1101/2021.04.17.440292 *co-corresponding authors. J. S. Khanduja, M. Motamedi. Protocol for the development and use of spike-in control for chromatin immunoprecipitation (ChIP) of chromatin-binding proteins. Star Protocol 2025. 6: 104007. J. S. Khanduja, M. Motamedi. Protocol for chromatin immunoprecipitation of chromatin-binding proteins in Schizosaccharomyces pombe using a dual-crosslinking approach. Star Protocol 2025. 6: 103695. Related Episodes Evolutionary Forces Shaping Mammalian Gene Regulation (Emily Wong) Chromatin Evolution (Arnau Sebé-Pedrós) The Role of lncRNAs in Tumor Growth and Treatment (Sarah Diermeier) 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
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    46 分
  • Evolutionary Forces Shaping Mammalian Gene Regulation (Emily Wong)

    Evolutionary Forces Shaping Mammalian Gene Regulation (Emily Wong)
    2025/09/18

    In this episode of the Epigenetics Podcast, we talked with Emily Wong from the University of New South Wales in Sydney about her work on how evolution shapes mammalian genes.

    As the head of the Regulatory Systems Lab at the Victor Chang Cardiac Research Institute and an associate professor at UNSW, Emily’s research centers on gene control and enhancers. We delve into her pivotal 2017 publication in Nature Communications, where she investigated transcription factor binding in liver-specific contexts, shedding light on the regulatory mechanisms at play in mammals.

    Emily elaborates on her postdoctoral work at the European Bioinformatics Institute and the innovative hybrid systems she used to dissect genetic variation effects, which allowed her to differentiate between cis-regulatory and trans-regulatory influences. By employing techniques like ChIP-seq, she was able to illustrate the combinatorial effects of transcription factors on gene expression, paving the way for her collaborative efforts across disciplines and organisms.

    We also examine Emily's findings regarding enhancer function through comparative studies between zebrafish and marine sponges. Using historical data on conserved genetic sequences, she and her team identified enhancer regions that displayed activity in specific vertebrate cell types, despite their evolutionary divergence from sponges. This unexpected result suggests deeper insights into how enhancers can be co-opted for new functions as species evolve.

    Furthermore, we dive into Emily's latest ventures involving advanced methodologies such as chromatin accessibility profiling with ATAC-seq and how these insights can elucidate the genomic landscape of metazoan embryogenesis. She highlights significant correlations between enhancer turnover and DNA replication timing, suggesting evolutionary implications that should be taken into account in future genomic studies.

    References

    • Wong, E. S., Zheng, D., Tan, S. Z., Bower, N. I., Garside, V., Vanwalleghem, G., Gaiti, F., Scott, E., Hogan, B. M., Kikuchi, K., McGlinn, E., Francois, M., & Degnan, B. M. (2020). Deep conservation of the enhancer regulatory code in animals. Science, 370(6517), eaax8137. https://doi.org/10.1126/science.aax8137

    • Cornejo-Páramo, P., Petrova, V., Zhang, X. et al. Emergence of enhancers at late DNA replicating regions. Nat Commun 15, 3451 (2024). https://doi.org/10.1038/s41467-024-47391-5

    Related Episodes

    • Ultraconserved Enhancers and Enhancer Redundancy (Diane Dickel)

    • Enhancer Communities in Adipocyte Differentiation (Susanne Mandrup)

    • Enhancer-Promoter Interactions During Development (Yad Ghavi-Helm)

    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
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    42 分
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