In this episode of the Epigenetics Podcast, we talked with Fides Zenk from the École polytechnique fédérale de Lausanne about her work on transgenerational inheritance in Drosophila and brain organoids for human development insights.

Dr. Zenk begins by sharing her journey into the field of biology, revealing her childhood fascination with nature and the intricate details of plant development. Her transition from an interest in ecology to a deep dive into molecular biology and gene regulation lays the groundwork for understanding her current research focus. We explore how her early experiences continue to shape her scientific curiosity, particularly her passion for studying cellular changes over time during embryonic development.

As the conversation progresses, Dr. Zenk paints a vivid picture of her work at EPFL, where she combines functional genomics, chromatin profiling, and molecular biology techniques. She elaborates on her initial research during her PhD with Nicola Iovino, where she investigated the transgenerational inheritance of histone modifications in Drosophila. This discussion includes fascinating insights into how histone modifications can carry information across generations and their implications in gene expression regulation during early embryonic stages.

Dr. Zenk also provides a glimpse into her postdoctoral work with Barbara Treutlein, where she shifted focus to human models and quantitative analysis using brain organoids. This segment of the episode reveals her commitment to translating molecular mechanisms to human health, especially in understanding the intricacies of brain development and neurogenesis. She describes how her team mapped dynamic changes in histone modifications during critical developmental stages, integrating various data modalities to build an intricate developmental atlas.

Zenk F, Loeser E, Schiavo R, et al. Germ line-inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition. Science (New York, N.Y.). 2017 Jul;357(6347):212-216. DOI: 10.1126/science.aam5339. PMID: 28706074.

Zenk F, Zhan Y, Kos P, et al. HP1 drives de novo 3D genome reorganization in early Drosophila embryos. Nature. 2021 May;593(7858):289-293. DOI: 10.1038/s41586-021-03460-z. PMID: 33854237; PMCID: PMC8116211.

Zenk F, Fleck JS, Jansen SMJ, et al. Single-cell epigenomic reconstruction of developmental trajectories from pluripotency in human neural organoid systems. Nature Neuroscience. 2024 Jul;27(7):1376-1386. DOI: 10.1038/s41593-024-01652-0. PMID: 38914828; PMCID: PMC11239525.

The Role of Small RNAs in Transgenerational Inheritance in C. elegans (Oded Rechavi)

Mapping the Epigenome: From Arabidopsis to the Human Brain (Joseph Ecker)

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In this episode of the Epigenetics Podcast, we talked with Anders Sejr Hansen from MIT about his work on the impact of 3D genome structures on gene expression, the roles of proteins like CTCF and cohesin, and advanced techniques like Region Capture Micro-C for mapping genome organisation.

Dr. Sejr Hansen introduces his research focusing on the relationship between three-dimensional genome structure and function, specifically how these structures can influence gene expression. He elaborates on the importance of transcription factors and the role of looping structures in gene regulation, emphasizing the implications of his work for understanding gene functionality in the context of both development and disease.

The conversation then shifts to discussing loop extrusion and the factors affecting loop stability, primarily CTCF and cohesin. Dr. Sejr Hansen highlights the dynamics of these proteins' binding interactions and how their speeds challenge the notion of stable looping structures in the genome. With a keen interest in CTCF's role, he explains how the protein interacts with DNA and the mechanistic aspects of transcription factor movement, alluding to research findings that reveal that CTCF and cohesin tend to form clusters which may play vital roles in establishing chromatin structure. As the interview progresses, Dr. Sejr Hansen details his transition to leading his own lab at MIT, emphasizing the continuation of his earlier work while expanding into new methodologies for studying chromatin. He underscores the importance of understanding not just the static structures of DNA interactions, but the dynamic nature of these relationships and how they influence gene expression. His lab's recent focus has included using advanced imaging techniques to assess the dynamics of chromatin interactions more precisely.

The discussion then touches on specific findings from Dr. Sejr Hansen's lab regarding the relationship between genome organization and double-strand break repair mechanisms. He emphasizes how the repair machinery can affect chromatin structure and underscores the essential role of cohesin in facilitating effective double-strand break repair by keeping broken DNA ends in proximity. He suggests that loop extrusion might help prevent genetic material from diffusing too far apart and improve the efficiency of repair.

Dr. Sejr Hansen also discusses innovations in genome mapping techniques, particularly the development of Region Capture Micro-C, which facilitates deeper insights into the three-dimensional organization of the genome. This method allows researchers to achieve significantly higher resolution in their analyses compared to traditional 3D genomics techniques like Hi-C. He outlines the technical process and the implications of their findings, especially regarding enhancer-promoter interactions and the surprisingly promiscuous nature of these relationships.

Anders S Hansen, Iryna Pustova, Claudia Cattoglio, Robert Tjian, Xavier Darzacq (2017) CTCF and cohesin regulate chromatin loop stability with distinct dynamics eLife 6:e25776 https://doi.org/10.7554/eLife.25776

Claudia Cattoglio, Iryna Pustova, Nike Walther, Jaclyn J Ho, Merle Hantsche-Grininger, Carla J Inouye, M Julius Hossain, Gina M Dailey, Jan Ellenberg, Xavier Darzacq, Robert Tjian, Anders S Hansen (2019) Determining cellular CTCF and cohesin abundances to constrain 3D genome models eLife 8:e40164 https://doi.org/10.7554/eLife.40164

Goel, V.Y., Huseyin, M.K. & Hansen, A.S. Region Capture Micro-C reveals coalescence of enhancers and promoters into nested microcompartments. Nat Genet 55, 1048–1056 (2023). https://doi.org/10.1038/s41588-023-01391-1

Biophysical Modeling of 3-D Genome Organization (Leonid Mirny)

Unraveling Mechanisms of Chromosome Formation (Job Dekker)

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In this episode of the Epigenetics Podcast, we talked with Vincent Pasque from KU Leuven about his work on the reprogramming of cell identity through epigenetic mechanisms, particularly during early development and cellular reprogramming.

We begin by tracing Vincent's journey into biology, sparked by early childhood experiences in nature and meaningful encounters with inspiring teachers. His fascination with the complexities of biology crystallized during a pivotal moment while listening to a radio segment on epigenetics in the late '90s, which led him to pursue studies in genetics and biochemistry. This formative path brought him to leading institutions, including the prestigious lab of John Gurdon, where he explored the phenomenon of nuclear reprogramming. Vincent recounts his early experiments that led to the discovery of macro H2A as a barrier to reprogramming, emphasizing the core challenge of erasing somatic cell identity.

As the conversation unfolds, Vincent introduces us to critical findings from his research. He shares how the inactive X chromosome serves as a compelling model to investigate epigenetic regulation, revealing that the dynamics of reprogramming and differentiation are far from simple reversals of development. He highlights the significant differences between male and female iPSCs and how X-linked genes influence DNA methylation and differentiation rates in these cells. The implications of these findings extend beyond developmental biology to inform our understanding of diseases, particularly cancer.

Transitioning to his current work, Vincent describes pioneering advances in characterizing the chromatin-associated proteome during the differentiation of human pluripotent stem cells. The surprising discovery of elevated histone modifications in naïve cells leads to intriguing questions about the barriers to cellular plasticity and the mechanisms by which cells resist alternative fate conversions. The potential applications of this research could reshape our approach to regenerative medicine and therapeutic interventions.

Pasque V, Gillich A, Garrett N, Gurdon JB. Histone variant macroH2A confers resistance to nuclear reprogramming. The EMBO Journal. 2011 May;30(12):2373-2387. DOI: 10.1038/emboj.2011.144. PMID: 21552206; PMCID: PMC3116279.

Jullien, J., Miyamoto, K., Pasque, V., Allen, G. E., Bradshaw, C. R., Garrett, N. J., Halley-Stott, R. P., Kimura, H., Ohsumi, K., & Gurdon, J. B. (2014). Hierarchical Molecular Events Driven by Oocyte-Specific Factors Lead to Rapid and Extensive Reprogramming. Molecular Cell, 55(4), 524–536. https://doi.org/10.1016/j.molcel.2014.06.024

Pasque V, Tchieu J, Karnik R, et al. X chromosome reactivation dynamics reveal stages of reprogramming to pluripotency. Cell. 2014 Dec;159(7):1681-1697. DOI: 10.1016/j.cell.2014.11.040. PMID: 25525883; PMCID: PMC4282187.

Zijlmans DW, Talon I, Verhelst S, et al. Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction. Nature Cell Biology. 2022 Jun;24(6):858-871. DOI: 10.1038/s41556-022-00932-w. PMID: 35697783; PMCID: PMC9203278.

The Discovery of Genomic Imprinting (Azim Surani)

Gene Expression Control and Intricacies of X-chromosome Inactivation (Claire Rougeulle)

Epigenetics and X-Inactivation (Edith Heard)

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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.

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

ATAC-Seq, scATAC-Seq and Chromatin Dynamics in Single-Cells (Jason Buenrostro)

Multiple challenges of ATAC-Seq, Points to Consider (Yuan Xue)

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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.

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.

Evolutionary Forces Shaping Mammalian Gene Regulation (Emily Wong)

Chromatin Evolution (Arnau Sebé-Pedrós)

The Role of lncRNAs in Tumor Growth and Treatment (Sarah Diermeier)

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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.

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

Ultraconserved Enhancers and Enhancer Redundancy (Diane Dickel)

Enhancer Communities in Adipocyte Differentiation (Susanne Mandrup)

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

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In this episode of the Epigenetics Podcast, we talked with Arnau Sebé-Pedrós from the Center for Genomic Regulation in Barcelona about his work on chromatin evolution.

The Interview starts by examining specific research findings, including his seminal 2018 paper demonstrating whole-organism single-cell transcriptomics to map larval and adult cell types in the model organism Nematostella vectensis. Dr. Sebe-Pedros recounted the challenges and triumphs faced when delving into single-cell studies of non-model organisms, revealing the innovative strategies employed in the lab to overcome these hurdles.

Shifting gears, we touched upon his work comparing cell types and molecular pathways in reef-building corals through single-cell RNA sequencing, contributing to our understanding of evolutionary conservation and divergence within the cnidarian lineage. We discussed how this comparative approach not only adds to knowledge about coral biology but also enhances methodological frameworks in ecological studies.

In addition, Dr. Sebe-Pedros shared insights into ongoing efforts to reconstruct eukaryotic chromatin evolution using comparative proteomics and genomics analysis, as well as the mechanisms of genomic regulation in various species. His reflections on the sharing of experimental insights across research groups illustrated the collaborative spirit prevalent in the scientific community, particularly regarding endeavors like the Biodiversity Cell Atlas consortium aimed at expanding single-cell efforts across the tree of life.

The episode culminated with Dr. Sebe-Pedros’s thoughts on the revolutionary impact of functional genomic technologies and the vast potential they hold for answering longstanding questions in evolutionary biology. With an emphasis on epigenetics, he defined this field as encompassing any information not encoded directly in the DNA, especially in its role in establishing cell identity and differentiation.

https://www.biodiversitycellatlas.org

Sebé-Pedrós, A., Saudemont, B., Chomsky, E., Plessier, F., Mailhé, M. P., Renno, J., Loe-Mie, Y., Lifshitz, A., Mukamel, Z., Schmutz, S., Novault, S., Steinmetz, P. R. H., Spitz, F., Tanay, A., & Marlow, H. (2018). Cnidarian Cell Type Diversity and Regulation Revealed by Whole-Organism Single-Cell RNA-Seq. Cell, 173(6), 1520–1534.e20. https://doi.org/10.1016/j.cell.2018.05.019

Sebé-Pedrós, A., Chomsky, E., Pang, K., Lara-Astiaso, D., Gaiti, F., Mukamel, Z., Amit, I., Hejnol, A., Degnan, B. M., & Tanay, A. (2018). Early metazoan cell type diversity and the evolution of multicellular gene regulation. Nature ecology & evolution, 2(7), 1176–1188. https://doi.org/10.1038/s41559-018-0575-6

Kim, I.V., Navarrete, C., Grau-Bové, X. et al. Chromatin loops are an ancestral hallmark of the animal regulatory genome. Nature 642, 1097–1105 (2025). https://doi.org/10.1038/s41586-025-08960-w

Evolutionary Epigenetic Clocks and Epigenetic Inheritance in Plants (Frank Johannes)

Neuroepigenetic Mechanisms and Primate Epigenome Evolution (Boyan Bonev)

Transposable Elements in Gene Regulation and Evolution (Marco Trizzino)

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In this episode of the Epigenetics Podcast, we talked with Luca Magnani from Institute of Cancer Research and UNIMI in Milan about his work on epigenetic mechanisms of drug resistance and cancer cell dormancy in breast cancer.

We start the interview by putting our focus on his significant contributions to the understanding of estrogen receptor-positive breast cancer. In a foundational study from 2013, Professor Magnani and his colleagues illuminated the role of genome-wide reprogramming of the chromatin landscape in conferring resistance to endocrine therapy. This research marked a departure from a purely genetic mutation paradigm, proposing instead that epigenetic modifications play a pivotal role in the development of drug resistance.

A fascinating part of our conversation centers on the role of pioneer transcription factors, particularly PBX1, in regulating the estrogen receptor's transcriptional response. Professor Magnani explains how PBX1, typically associated with hematopoietic development, influences estrogen receptor activity, thereby shaping the cancer cell's fate and response to treatment.

Continuing our exploration, we discuss the critical distinctions between primary and metastatic breast cancer through the lens of epigenetic reprogramming. By analyzing samples from women with breast cancer, Professor Magnani's work identifies specific enhancer usage that marks the transition to a drug-resistant state which was a breakthrough in linking epigenetic alterations to real-world patient outcomes. He emphasizes that the reliance on genetic mutations alone does not adequately explain the mechanisms of drug resistance, pushing the field to consider the epigenetic landscape more deeply.

Our conversation also touches on the evolution of experimental techniques. Professor Magnani shares insights into the transition from traditional ChIP-seq methods to CUT&RUN, demonstrating the need for techniques that cater to the limited material available from clinical samples. This adaptability mirrors the dynamic nature of cancer itself, as cells continuously evolve under therapeutic pressure.

As we traverse through the complexities of dormancy and reactivation in cancer cells, Professor Magnani enlightens us on the unpredictable nature of tumor behavior. He describes how cancer cells can enter dormant states and how their awakening is influenced by environmental factors, akin to an evolutionary response to stressors, thus revealing the intricate balance between survival and proliferation.

In the latter part of the episode, we explore Professor Magnani's vision for the future of breast cancer research, which includes the need for better animal models that mimic human disease. His pursuit of understanding estrogen receptor behavior both in healthy and cancerous cells reflects a holistic approach to cancer biology, aiming to decipher the transition from normal tissue to malignancy.

Magnani, L., Stoeck, A., Zhang, X., Lánczky, A., Mirabella, A. C., Wang, T. L., Gyorffy, B., & Lupien, M. (2013). Genome-wide reprogramming of the chromatin landscape underlies endocrine therapy resistance in breast cancer. Proceedings of the National Academy of Sciences of the United States of America, 110(16), E1490–E1499. https://doi.org/10.1073/pnas.1219992110

Nguyen, V. T., Barozzi, I., Faronato, M., Lombardo, Y., Steel, J. H., Patel, N., Darbre, P., Castellano, L., Győrffy, B., Woodley, L., Meira, A., Patten, D. K., Vircillo, V., Periyasamy, M., Ali, S., Frige, G., Minucci, S., Coombes, R. C., & Magnani, L. (2015). Differential epigenetic reprogramming in response to specific endocrine therapies promotes cholesterol biosynthesis and cellular invasion. Nature communications, 6, 10044. https://doi.org/10.1038/ncomms10044

Patten, D. K., Corleone, G., & Magnani, L. (2018). Chromatin Immunoprecipitation and High-Throughput Sequencing (ChIP-Seq): Tips and Tricks Regarding the Laboratory Protocol and Initial Downstream Data Analysis. Methods in molecular biology (Clifton, N.J.), 1767, 271–288. https://doi.org/10.1007/978-1-4939-7774-1_15

Enhancers and Chromatin Remodeling in Mammary Gland Development (Camila dos Santos)

Contribution of Estrogen Receptor to Breast Cancer Progression (Jason Carroll)

Circulating Epigenetic Biomarkers in Cancer (Charlotte Proudhon)

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In this episode of the Epigenetics Podcast, we talked with Erica Korb from the University of Pennsylvania about her work on BRD4 and the histone variant H2BE, which influences synaptic genes and neuronal activity.

Dr. Korb discusses the focus of her lab, which centers on epigenetic mechanisms impacting gene regulation in neurons. Her research primarily examines histone biology and its connection to neurodevelopmental disorders, including autism spectrum disorder and intellectual disabilities. Dr. Korb expounds on the collaborative environment at UPenn’s Epigenetics Institute, emphasizing how the rich diversity of research topics fosters innovative ideas and projects within the community.

Reflecting on her earlier work from her postdoctoral studies, Dr. Korb discusses her first significant findings regarding the protein BRD4. This work demonstrated BRD4's role in mediating transcriptional regulation crucial for learning and memory processes. She explains how disrupting this protein's function in neurons hindered critical gene activations required for memory formation in mice. This foundational understanding opened avenues for exploring the broader implications of chromatin regulation in various neurodevelopmental conditions.

Transitioning into her current research endeavors, Dr. Korb reveals how she aims to expand her focus beyond Fragile X syndrome. With her lab now investigating multiple chromatin regulators implicated in various forms of autism spectrum disorders, she describes a recent project where RNA sequencing exposed substantial overlaps in gene expression changes associated with five distinct chromatin modifiers, each contributing uniquely to neuronal function while collectively demonstrating sensitivity to chromatin disruptions.

A significant portion of the discussion centers around Dr. Korb’s unexpected exploration into how COVID-19 intersects with chromatin biology through a phenomenon known as histone mimicry. Leveraging bioinformatic tools during the pandemic, her lab discovered that certain viral proteins mimic histone sequences, which may lead to altered transcriptional outputs in host cells. This coincidental finding illustrates both the creative adaptability needed in scientific research and the importance of collaborative efforts across disciplines to uncover new insights.

The conversation also delves into Dr. Korb’s recent work regarding the histone variant H2BE, initiated by one of her graduate students. She explains how prior research only recognized H2BE's expression in the olfactory system, yet her lab has demonstrated its significant role in regulating synaptic genes and memory formation throughout broader neuronal contexts. Notably, they identified a single amino acid change that influences H2BE's function in chromatin accessibility and gene transcription, emphasizing its potential evolutionary conservation across species.

In terms of H2BE's role, Dr. Korb elucidates that its activity is integral in response to extracellular stimuli, particularly within the context of neuronal activation. Intriguingly, they found that H2BE expression decreases in reaction to long-term neuronal stimulation, suggesting a complex mechanism of homeostatic plasticity crucial for regulating neuronal activity levels. This research not only advances understanding of chromatin dynamics but also holds implications for neuronal health and disease mechanisms.

Feierman, E. R., Louzon, S., Prescott, N. A., Biaco, T., Gao, Q., Qiu, Q., Choi, K., Palozola, K. C., Voss, A. J., Mehta, S. D., Quaye, C. N., Lynch, K. T., Fuccillo, M. V., Wu, H., David, Y., & Korb, E. (2024). Histone variant H2BE enhances chromatin accessibility in neurons to promote synaptic gene expression and long-term memory. Molecular cell, 84(15), 2822–2837.e11. https://doi.org/10.1016/j.molcel.2024.06.025

Korb, E., Herre, M., Zucker-Scharff, I., Gresack, J., Allis, C. D., & Darnell, R. B. (2017). Excess Translation of Epigenetic Regulators Contributes to Fragile X Syndrome and Is Alleviated by Brd4 Inhibition. Cell, 170(6), 1209–1223.e20. https://doi.org/10.1016/j.cell.2017.07.033

Kee, J., Thudium, S., Renner, D. M., Glastad, K., Palozola, K., Zhang, Z., Li, Y., Lan, Y., Cesare, J., Poleshko, A., Kiseleva, A. A., Truitt, R., Cardenas-Diaz, F. L., Zhang, X., Xie, X., Kotton, D. N., Alysandratos, K. D., Epstein, J. A., Shi, P. Y., Yang, W., … Korb, E. (2022). SARS-CoV-2 disrupts host epigenetic regulation via histone mimicry. Nature, 610(7931), 381–388. https://doi.org/10.1038/s41586-022-05282-z

Feierman, E. R., Paranjapye, A., Su, S., Qiu, Q., Wu, H., & Korb, E. (2024). Histone variant H2BE controls activity-dependent gene expression and homeostatic scaling. bioRxiv : the preprint server for biology, 2024.11.01.620920. https://doi.org/10.1101/2024.11.01.620920

Neuroepigenetic Mechanisms and Primate Epigenome Evolution (Boyan Bonev)

DNA Methylation Alterations in Neurodegenerative Diseases (Paula Desplats)

The Role of Histone Dopaminylation and Serotinylation in Neuronal Plasticity (Ian Maze)

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In this episode of the Epigenetics Podcast, we talked with Dr. Joseph Ecker from the Salk Institute about his work on high-resolution genome-wide mapping technologies, specifically how the regulation of gene expression is influenced by DNA methylation, chromatin accessibility, and non-coding RNAs across various cell types and developmental stages.

During our conversation, we delve into Dr. Ecker's contributions to the characterization of the genome of Arabidopsis thaliana, a project pivotal in the plant genomics field, where he collaborated on the early sequencing efforts that dramatically outpaced expectations. He highlights the technological advancements that enabled such efficient sequencing and how this foundational work opened new avenues for exploring transcriptional activity.

We also discuss Dr. Ecker’s pivotal work on the comprehensive DNA methylation map of Arabidopsis, which he developed in collaboration with other researchers. This groundbreaking study established the links between methylation patterns and gene expression, paving the way for further research into how these epigenetic marks influence over gene regulation. He elaborates on the significance of transitioning from traditional methods to more sophisticated techniques, such as RNA-seq, and the lessons learned from sequencing projects that have since been applied to human biology.

Dr. Ecker's transition to studying human cells is further explored as he discusses the profiling of DNA methylation in induced pluripotent stem cells (iPSCs), revealing how epigenetic memory can influence cellular differentiation and development. He underscores the importance of understanding these methylation patterns, particularly as they relate to conditions like Alzheimer's disease and stem cell biology, where he examines potential applications of his findings in medical research.

As our conversation progresses, we touch upon Dr. Ecker's ongoing projects that utilize advanced multi-omic techniques to investigate the epigenomes of the human brain, focusing on how DNA methylation and gene expression change with age and in the context of neurodegenerative diseases. He details the collaboration efforts with various consortia aimed at cataloging gene regulatory networks and understanding the complex interactions that take place within the brain throughout different life stages.

Mozo T, Dewar K, Dunn P, Ecker JR, Fischer S, Kloska S, Lehrach H, Marra M, Martienssen R, Meier-Ewert S, Altmann T. A complete BAC-based physical map of the Arabidopsis thaliana genome. Nat Genet. 1999 Jul;22(3):271-5. doi: 10.1038/10334. PMID: 10391215.

Zhang X, Yazaki J, Sundaresan A, Cokus S, Chan SW, Chen H, Henderson IR, Shinn P, Pellegrini M, Jacobsen SE, Ecker JR. Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis. Cell. 2006 Sep 22;126(6):1189-201. doi: 10.1016/j.cell.2006.08.003. Epub 2006 Aug 31. PMID: 16949657.

Lister R, O'Malley RC, Tonti-Filippini J, Gregory BD, Berry CC, Millar AH, Ecker JR. Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell. 2008 May 2;133(3):523-36. doi: 10.1016/j.cell.2008.03.029. PMID: 18423832; PMCID: PMC2723732.

Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009 Nov 19;462(7271):315-22. doi: 10.1038/nature08514. Epub 2009 Oct 14. PMID: 19829295; PMCID: PMC2857523.

Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, Antosiewicz-Bourget J, O'Malley R, Castanon R, Klugman S, Downes M, Yu R, Stewart R, Ren B, Thomson JA, Evans RM, Ecker JR. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature. 2011 Mar 3;471(7336):68-73. doi: 10.1038/nature09798. Epub 2011 Feb 2. Erratum in: Nature. 2014 Oct 2;514(7520):126. PMID: 21289626; PMCID: PMC3100360.

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Email: [email protected]