Active Motif's Podcast

In this episode of the Epigenetics Podcast, we caught up with Vladimir Teif from the University of Essex to talk about his work on nucleosome positioning in development and disease. Vladimir's research has been pivotal in understanding nucleosome positioning and its implications for cell differentiation, particularly in embryonic stem cells and cancer. We discuss his groundbreaking studies that first mapped nucleosome positions in various cell types and how these findings led to uncovering the intricate relationships between nucleosome stability, transcription factors, and DNA modifications such as methylation. This understanding has immense significance for cancer diagnostics, where knowing the spatial arrangement of nucleosomes could influence how aggressive a cancer type might be, or how a patient might respond to treatment. Transitioning from foundational research to clinical applications, Vladimir elaborates on his exciting work with liquid biopsies. By analyzing cell-free DNA from blood plasma, research

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 amplif

In this episode of the Epigenetics Podcast, we talked with Christa Buecker from the Max Perutz Laboratories in Vienna about her work on transcriptional regulation during early embryonic development. Dr. Buecker unravels the differences between naive and primed pluripotency states, showcasing how OCT4 relocalization and enhancer chromatin landscapes play pivotal roles during this transition. The conversation delves into the intricate interplay of transcription factors like OCT4 and OTX2, shedding light on their collaborative efforts in regulating gene expression during differentiation. Dr. Buecker then shares insights from her study on enhancer elements controlling FGF5 expression and discusses the surprising revelation that individual enhancers show no intrinsic activity but work together in a super additive fashion. She also touches upon her research on IRF1's connection to the gene regulatory network and its role in protecting cells against viral infections. The conversation shifts to Dr. Buecker's current

In this episode of the Epigenetics Podcast, we talked with Claire Rougeulle from the Epigenetics and Cell Fate Center at Université Paris City about her work on gene expression control, the intricacies of X-chromosome inactivation, and the potential of non-coding RNAs in this process. In this episode Claire Rougeulle explains her discoveries regarding the transcription regulation of XIST by factors like YY1 and the erosion of X-chromosome inactivation in human pluripotent stem cells. She shares the complexity of distinguishing between epigenetics and transcriptional regulation, highlighting the challenges in studying allelic expression of X-chromosomes at the single-cell level. The Episode further explores Claire's findings on the XACT locus regulation, evolution from retroviruses, and its potential role in preventing X-chromosome silencing. Claire also shares her future research focus on understanding X-inactivation establishment in humans and the transition from XIST attenuating to silencing X-chromosomes a

In this episode of the Epigenetics Podcast, we talked with James Hackett from the EMBL in Rome about his work on epigenetic mechanisms in genome regulation and developmental programming. One of James Hackett's significant studies focused on DNA methylation and genome defense mechanisms in the germline, exploring the role of chromatin modifications in mammalian gene regulation. He delves into investigating the erasure of DNA methylation in the germline, highlighting the key role of the TET-enzymes in demethylation processes. Dr. Hackett shares insights from his research on pluripotent stem cells, where he mapped genome-wide DNA methylation and hydroxymethylation in different pluripotent states. He discusses the impact of extrinsic conditions on pluripotent states and the biases observed in lineage preferences. Furthermore, the discussion delves into the development of a CRISPR screening tool to study cell fate transitions, particularly focusing on the genetic factors contributing to germline specification. He

In this episode of the Epigenetics Podcast, we talked with Lothar Schermelleh from the University of Oxford about his work on advanced optical imaging in 3D nuclear organisation.  The interview starts by Lothar Schermelleh sharing his groundbreaking work in understanding chromatin organization using super-resolution microscopy techniques. He then delves into his past experiments, including his publication on imaging chromatin domains and X chromosome inactivation. His work showcases the power of structured illumination microscopy in overcoming diffraction limits, revealing insights into nuclear organization and regulation. Lothar also discusses refining methods for labeling chromosome territories and replication domains, as well as exploring structural and functional nuclear organization using advanced microscopy techniques. They touch on the potential of AI in microscopy, the importance of quality control in imaging, and Lothar's grant proposal for developing artifact-free, super-resolution imaging under c

In this episode of the Epigenetics Podcast, we talked with Dr. Stephan Hamperl from the Helmholtz Zentrum Munich about his work on how conflicts between transcription, replication, and R-loop formation influence genome stability in human cells. During the early stages of his career Stephan studied conflicts between transcription and replication in human cells, particularly focusing on R-loop structures. In our discussion, he explains the formation of R-loops and their impact on genome stability, emphasizing the importance of the orientation of replication forks approaching R-loops in determining DNA damage outcomes. Stephan then delves into his work on the MATAC-Seq method, which analyzes chromatin domains at DNA replication origins to understand replication timing variability. The method involves methylating DNA linkers between nucleosomes and using nanopore sequencing for single-molecule readouts, revealing heterogeneity in chromatin structure at replication origins. Finally, Stephan discusses his automated

In this episode of the Epigenetics Podcast, we talked with Nadav Ahituv from University of California, San Francisco about his work on mutations of gene regulatory elements in human disease. Using massively parallel experiments, his lab revolutionized functional genomics by studying the impact of transcription factor binding sites on gene expression. His groundbreaking technology deciphered the regulatory language of gene expression by exploring transcription factor combinations, spacing, and orientation. By delving into the influence of DNA shape and gene topology, Nadav Ahituv's research provides a comprehensive understanding of gene regulation at the molecular level, shedding light on the complexity of genetic interactions. The conversation delves into specific cases involving enhancers, gene sequencing, and 3D genomic structure, highlighting the impact of critical elements such as CTCF sites on gene expression. Discussions of haploid insufficiency and its implications for human health, using CRISPR techno

In this episode of the Epigenetics Podcast, we talked with Ana Cvejic from the Biotech Research & Innovation Centre at the University of Copenhagen about her work on using sc-multiomics to characterise human developmental hematopoiesis. The conversation starts by delving into Ana's research on hematopoiesis, starting with her work on identifying novel genes controlling blood traits in zebrafish models. She explains her transition to single-cell methodologies and the application of single-cell RNA sequencing to study hematopoietic cells in zebrafish, focusing on thrombocyte lineage commitment and gene expression. The discussion progresses to her groundbreaking study on human fetal hematopoiesis, where she combined single-cell RNA-seq with single-cell ATAC-seq to understand chromatin accessibility and gene expression dynamics. Ana then shares insights into the identification of new cell surface markers and the priming of hematopoietic stem cells, particularly in conditions like Down syndrome. Furthermore, s

In this episode of the Epigenetics Podcast, we talked with Sven Heinz from the University of California in San Diego about his work on the impact of sequence variation on transcription factor binding affinities and genetic diversity. Sven Heinz talks about a landmark study published in Nature that examined the impact of sequence variation on transcription factor binding affinities and downstream effects on gene expression. Modifying genetic sequences to understand the influence of different motifs provided valuable insights into how genetic variation shapes cellular responses and gene expression patterns, underscoring the importance of genetic diversity. Methodological approaches using inducible systems to observe changes in transcription factor binding patterns highlight the critical role of motif variation and redundancy in transcription factor families. These studies provide essential insights into the complex network of transcriptional regulation and chromatin dynamics, revealing the nuanced mechanisms th

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.  

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 proces

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 r

In this episode of the Epigenetics Podcast, we talked with Weiwei Dang from Baylor College of Medicine about his work on molecular mechanisms of aging and the role of H3K36me3 and cryptic transcription in cellular aging. The team in the Weiwei Dang lab explored the connection between histone marks, specifically H4K16 acetylation and H3K36 methylation, and aging. Dr. Dang describes how the lab conducted experiments by mutating H4K16 to determine its effect on lifespan. They observed that the mutation to glutamine accelerated the aging process and shortened lifespan, providing causal evidence for the relationship between H4K16 and lifespan. They also discovered that mutations in acetyltransferase and demethylase enzymes had opposite effects on lifespan, further supporting a causal relationship. Weiwei Dang then discusses their expanded research on aging, conducting high-throughput screens to identify other histone residues and mutants in yeast that regulate aging. They found that most mutations at K36 shortened

In this episode of the Epigenetics Podcast, we talked with Mitch Guttman from California Institute of Technology about his work on characterising the 3D interactions of the genome using Split-Pool Recognition of Interactions by Tag Extension (SPRITE). Mitch Guttman discusses his exploration of the long non-coding RNA Xist, which plays a crucial role in X chromosome inactivation. He explains how they discovered that Xist is present everywhere in the nucleus, not just in specific locations on the X chromosome. Through their research, they identified critical proteins like SHARP that are involved in X chromosome silencing. The discussion then shifts to SPRITE, a method they developed to map multi-way contacts and generalize beyond DNA to include RNA and proteins. They compare SPRITE to classical proximity ligation methods like Hi-C and discuss how cluster sizes in SPRITE can estimate 3D distances between molecules. The conversation also touches upon the potential of applying SPRITE to single-cell experiments, al

In this episode of the Epigenetics Podcast, we talked with Yali Dou from Keck School of Medicine of USC about her work on MLL Proteins in Mixed-Lineage Leukemia. To start off this Interview Yali describes her early work on MLL1 and its function in transcription, particularly its involvement in histone modification. She explains her successful purification of the MLL complex and the discovery of MOF as one of the proteins involved. Next, the interview focuses on her work in reconstituting the MLL core complex and the insights gained from this process. She shares her experience of reconstituting the MLL complex and discusses her focus on the crosstalk of H3K4 and H3K79 methylation, regulated by H2BK34 ubiquitination. The podcast then delves into the therapeutic potential of MLL1, leading to the discovery of a small molecule inhibitor. Finally, we talk about the importance of the protein WDR5 in the assembly of MLL complexes and how targeting the WDR5-ML interaction can inhibit MLL activity.   References Dou, Y

In this episode of the Epigenetics Podcast, we talked with Sam Buckberry from the Telethon Kids Institute about his work on gene imprinting, sex-biased gene expression, DNA regulatory landscapes, and genomics in the indigenous population of Australia. Sam Buckberry's research career started with working on the imprinting of H19, IGF2, and IGF2R genes in the placenta. We talk about the controversy surrounding the imprinting of IGF2R and how his study used pyrosequencing to quantify gene expression. We also discuss Sam's work on sex-biased gene expression in the placenta and the identification of a cluster of genes related to placental development and pregnancy. In addition, we talk about Sam's research on reprogramming and the characterization of DNA regulatory landscapes during the process. We discuss the challenges of working with sequencing data, the discovery of epigenetic memories, and erasing them during reprogramming. Towards the end of the conversation, Sam mentions his current work in setting up an ep

In this episode of the Epigenetics Podcast, we talked with Kyle Eagen from Baylor College of Medicine about his work on BET Proteins and their role in chromosome folding and compartmentalization. In the early days of his research career Dr. Eagen made use of genomics and microscopy to study chromosomes, particularly polytene chromosomes in Drosophila. The correlation between the folding patterns detected by Hi-C and polytene bands highlights the similarities between the two, bridging traditional cytology with modern NGS methods. This work formed the basis of Kyle's thesis and sparked his interest in nuclear organization and chromosome 3D structure. In his independent lab Kyle then studied compartments in chromatin structure and focused on the relationship between histone modifications and the 3D structure of chromosomes. The discovery of BRD4-NUT, a fusion oncoprotein that reprograms chromosome 3D structure, is highlighted as a significant step forward in understanding chromatin structure. The conversation th

In this episode of the Epigenetics Podcast, we talked with Francesca Telese from UC San Diego and Jessica Zhou from Cold Spring Harbour about their work on the molecular underpinnings of human addiction. Francesca Telese worked on neuronal enhancers and their pivotal role in governing gene activity. She sheds light on her remarkable findings concerning the epigenetic signature of neuronal enhancers that are intricately involved in synaptic plasticity. Jessica Zhou joined Francesca Telese's lab as a PhD student where she worked on elucidating the effects of chronic cannabis use on memory and behavior in mice. She takes us through the fascinating correlation between THC and gene co-expression networks. Francesca and Jessicathen discuss the utilization of genetically diverse outbred rats in their research, along with the crucial exploration of cell type specificity in gene expression studies. They then delve into the long-term changes that occur in the brain after drug exposure and the profound implications for

In this episode of the Epigenetics Podcast, we talked with Tanja Vogel from the University Clinics Freiburg about her work on epigenetic modifications in stem cells during central nervous system development. During our discussion, Dr. Vogel shared that she and her team have investigated H3K79 methylation and its functional significance, which remains a topic of debate in the scientific community. They’ve also investigated the role of DOT1L in neural development and its implications for neuronal networks, as disrupting DOT1L can lead to conditions such as epilepsy and schizophrenia. They explored the function of the SOX2 enhancer in the presence or absence of DOT1L enzymatic inhibition. The conversation then shifts to FoxG1, a vital player in forebrain development. The team uncovered its role in chromatin accessibility and its connection to microRNA processing. Their study, utilizing ChIP-Seq, reveals FoxG1's interactions with enhancer regions and other transcription factors, like NeuroD1.   ### References Br