Active Motif's Podcast

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

In this episode of the Epigenetics Podcast, we talked with Maria Gambetta from the University of Lausanne about her work on the function of insulators in 3D genome folding. Maria Gambetta focuses on investigating 3D contact dynamics between enhancers and promoters, providing insights into tissue-specific gene activation. The team used capture-C to analyze dynamic looping events, emphasizing the significance of accessible chromatin peaks in enhancer-promoter interactions. Furthermore, they focused on gene insulation and CTCF's role in forming topologically associating domains in Drosophila. Hi-C analysis on CTCF mutants revealed the conservation of TAD boundary mechanisms, identifying CP-190 as a potential binding protein. Their findings on the loss of TAD boundaries in mutants and the role of transcription in TAD boundary formation are discussed as well as the function of CP190 and insulators in preventing interactions between promoters and enhancers. Their work challenges existing models of insulator functio

In this episode of the Epigenetics Podcast, we talked with Jason Carroll from the Cambridge Research Institute about his work on contribution of estrogen receptor to breast cancer progression. The Podcast centers around the crucial role of the forkhead protein FOXA1 in breast cancer. FOXA1 acts as a pioneer transcription factor, facilitating gene regulation by recruiting nuclear receptors to chromatin, profoundly influencing gene expression in various breast cancer subtypes. The FOXA1-positive subtype of triple-negative breast cancer, despite being estrogen receptor-negative, shares gene expression profiles with estrogen receptor-positive breast cancer, shedding light on the importance of targeting the androgen receptor for treatment. The challenges of studying transcription factor mappings from clinical samples are explored, with a focus on the ChIP-seq method's success in mapping estrogen receptor binding sites. Various techniques for transcription factor mapping, including CUT&RUN, CUT&Tag, and ChI

In this episode of the Epigenetics Podcast, we caught up with Sheila Teves from the University of British Columbia to talk about her work on the inheritance of transcriptional memory by mitotic bookmarking. Early in her research career, Sheila Teves focused on the impact of nucleosomes on torsional stress and gene regulation. She also highlights the development of a genome-wide approach to measure torsional stress and its relationship to nucleosome dynamics and RNA polymerase regulation. The conversation then shifts to her focus on transcriptional memory and mitotic bookmarking during her postdoc in the Tijan lab. She explores the concept of mitotic bookmarking, whereby certain transcription factors remain bound to their target sites during mitosis, facilitating efficient reactivation of transcription after cell division. She discusses her findings on the behavior of transcription factors on mitotic chromosomes, challenging the notion that they are excluded during mitosis. She also discusses the differences i

In this episode of the Epigenetics Podcast, we talked with Janine La Salle from UC Davis about her work on differential methylated regions in autism spectrum disorders. In our discussion, Janine LaSalle highlights her work on the placental epigenetic signature, which offers insights into the impact of fetal exposures and gene-environment interactions during the perinatal period. She emphasizes the placenta's value as a surrogate tissue for understanding human diseases. Her research on DNA methylation in the placenta across different mammalian species reveals consistent patterns in partially methylated and highly methylated domains. She explains the critical role of higher methylation levels in specific regions for gene expression and how this knowledge helps trace the placenta's developmental history. The conversation then delves into Dr. LaSalle's research on the link between placental DNA methylation and autism. Through epigenome-wide association studies, she discovered a novel autism gene and explored the

In this episode of the Epigenetics Podcast, we caught up with Björn Schumacher from the Institute for Genome Stability in Ageing and Disease at the University of Cologne to talk about his work on DNA damage in longevity and ageing. In this episode Björn Schumacher discusses his research on DNA repair and its impact on ageing. We explore his insights on the effects of DNA damage on transcription, the importance of studying development, and the role of histone modifications. We also discuss paternal DNA damage inheritance and the DREAM complex as a master regulator of DNA repair. The lab’s goal is to enhance somatic DNA repair for healthier ageing and disease prevention.   References Schumacher, B., van der Pluijm, I., Moorhouse, M. J., Kosteas, T., Robinson, A. R., Suh, Y., Breit, T. M., van Steeg, H., Niedernhofer, L. J., van Ijcken, W., Bartke, A., Spindler, S. R., Hoeijmakers, J. H., van der Horst, G. T., & Garinis, G. A. (2008). Delayed and accelerated aging share common longevity assurance mechanisms

In this episode of the Epigenetics Podcast, we talked with Capucine van Rechem from Stanford University about her work on the impact of chromatin modifiers on disease development and progression. During her postdoctoral work, Capucine van Rechem studied the effects of Single nucleotide polymorphisms (SNPs) in KDM4A on lung cancer cell lines and discovered a link between KDM4A and mTOR. She found that cells with the SNP had decreased KDM4A levels and increased sensitivity to inhibitors of the translation pathway. In addition, she found that a combination of histone marks was more predictive of replication timing than RNA expression alone, and identified the specific stages of the cell cycle where KDM4 primarily acts. Now in her own lab, the focus of her work shifted to SWI-SNF. The team has discovered the role of SWI-SNF in translation through polysome profiling and confirmed the interaction between SWI-SNF and translation. They are currently working to understand the functions of different complexes in tran

In this episode of the Epigenetics Podcast, we caught up with Luca Giorgetti from the Friedrich Miescher Institute to hear about his work on long-range transcriptional control by 3D chromosome structure. Luca Giorgetti's research focuses on chromosomal interactions, transcriptional output, and the dynamics of enhancer-promoter relationships. His lab investigated the causal relationship between chromosome interactions and transcriptional events. They’ve found that by manipulating the contact probabilities between an enhancer and a promoter by changing their distance, these changes had a substantial effect on transcription levels. This project was an experiment that Luca Giorgetti was eager to do, and it allowed him to establish a smooth functional relationship between contact probabilities and changes in transcription levels.   References Giorgetti, L., Galupa, R., Nora, E. P., Piolot, T., Lam, F., Dekker, J., Tiana, G., & Heard, E. (2014). Predictive polymer modeling reveals coupled fluctuations in chrom

In this episode of the Epigenetics Podcast, we talked with Mary Gehring from MIT about her work on transgenerational inheritance and epigenetic imprinting in plants. Mary Gehring and her team are focusing on plant epigenetics and genetic imprinting in plants, studying DNA methylation in Arabidopsis. They have found significant differences in DNA methylation between the embryo and endosperm of plants, particularly in relation to imprinted genes. She also discusses their work on hydroxymethylcytosine (5-hmC) in Arabidopsis and the challenges of detecting and studying this epigenetic modification. Next, we discuss the regulatory circuit involving ROS1, a DNA glycosylase involved in demethylation, and its role in maintaining epigenetic homeostasis. The interview concludes with a discussion of CUT&RUN, which the lab has adapted for use in plants. Due to its low input requirements this method has been valuable in studying various plant tissues and has influenced Mary Gehring's research on imprinting in Arabidop

In this episode of the Epigenetics Podcast, we talked to Claudio Cantù from Linköping University about his work on peak blacklists, peak concordance and what is a peak in CUT&RUN. Our host Stefan Dillinger and guest Claudio Cantù dive into the topic of when we can be sure that a peak is a peak. To help with this, Claudio Cantù's group has been working on defining a set of suspicious peaks that can be used as a "peak blacklist" and can be subtracted to clean up CUT&RUN data sets. The lab also worked on a method called ICEBERG (Increased Capture of Enrichment By Exhaustive Replicate aGgregation) to help define peaks from a number of experimental replicates. By using this algorithm, the team is trying to discover the beta-catenin binding profile, not the tip of the beta-catenin binding iceberg, but the whole of the beta-catenin binding profile.   References Zambanini, G., Nordin, A., Jonasson, M., Pagella, P., & Cantù, C. (2022). A new CUT&RUN low volume-urea (LoV-U) protocol optimized for trans

In this episode of the Epigenetics Podcast, we talked with Alistair Boettiger from Stanford University about his work on the analysis of 3D chromatin structure of single cells using super-resolution imaging. Alistair Boettiger and his team focus on developing advanced microscopy techniques to understand gene regulation at the level of 3D genome organization. They have developed Optical Reconstruction of Chromatin Architecture (ORCA), a microscopy approach to trace the 3-dimensional DNA path in the nucleus with genomic resolution down to 2 kb and a throughput of ~10,000 cells per experiment. These methods enable the identification of structural features with comparable resolution to Hi-C, while the advantages of microscopy such as single cell resolution and multimodal measurements remain.   References Boettiger, A., Bintu, B., Moffitt, J. et al. Super-resolution imaging reveals distinct chromatin folding for different epigenetic states. Nature 529, 418–422 (2016). https://doi.org/10.1038/nature16496 Bogdan

In this episode of the Epigenetics Podcast, we caught up with Claudia Keller Valsecchi from the Institute for Molecular Biology in Mainz to talk about her work on gene dosage alterations in evolution and ageing. Claudia Keller-Valsecchi's team focuses on understanding the fundamental mechanisms of how cellular function in eukaryotes is influenced by gene copy number variation. Recent findings indicate that precise MSL2-mediated gene dosage is highly relevant for organismal development. Since 2020 Claudia Keller-Valsecchi runs her own lab at the IMB in Mainz, Germany, where she tries to understand from a molecular mechanistic point of view how gene dosage compensation works, with projects in mosquitoes and in Artemia franciscanagene, as well as dosage regulation in the mammalian system regarding development and disease.   References Keller, C., Adaixo, R., Stunnenberg, R., Woolcock, K. J., Hiller, S., & Bühler, M. (2012). HP1Swi6 Mediates the Recognition and Destruction of Heterochromatic RNA Transcripts.

In this episode of the Epigenetics Podcast, we caught up with Lucas Farnung from Harvard Medical School to talk about his work on the structural analysis of nucleosomes during transcription. Lucas Farnung started his scientific career in Patrick Cramer's lab, trying to solve the crystal structure of RNA polymerase II transcribing through a nucleosome. This project spanned some time before being published in 2022, during which time Dr. Farnung accomplished several other goals. The team solved the cryo-electron microscopy structure of Chd1 from the yeast Saccharomyces cerevisiae bound to a nucleosome at a resolution of 4.8 Å, solved the structure of the nucleosome-CHD4 chromatin remodeler, and investigated the structural basis of nucleosome transcription mediated by Chd1 and FACT. In 2020, he started his own lab and is now working on structural analysis of nucleosomes during transcription and how chromatin remodelers work on the chromatin template. References Farnung, L., Vos, S. M., Wigge, C., & Cramer, P

In this episode of the Epigenetics Podcast, we caught up with Paula Desplats from the University of California San Diego to talk about her work on DNA Methylation Alterations in Neurodegenerative Diseases. The laboratory of Paula desalts focuses on decoding the role of epigenetic mechanisms, like DNA methylation, on the onset and progression of neurodegenerative diseases like Parkinson’s and Alzheimer’s. In doing so, on of the goals of the Desplats team is to develop a biomarker panel based on quantification of DNA methylation of selected genes that can discriminate Parkison's Disease patients from healthy subjects in a simple blood test. More recently, the team also focused on the role of the circadian rhythm on neurodegenerative diseases and finding a way how interventions can help in managing the disease.   References Masliah, E., Dumaop, W., Galasko, D., & Desplats, P. (2013). Distinctive patterns of DNA methylation associated with Parkinson disease: identification of concordant epigenetic changes i

In this episode of the Epigenetics Podcast, we caught up with Jop Kind from Hubrecht Institute to talk about his work on single cell DamID, EpiDamID, and Lamina Associated Domains (LADs). Jop Kind started out developing single cell DamID (scDamID), based on the DamID technique. First, this technique was adapted to a microscopic readout which enabled them to follow the localisation of chromatin domains after cell division. Next, the lab expanded this technique into the NGS space and created genome-wide maps of nuclear lamina Interactions in single human cells. Since LADs are in a heterochromatic chromatin context, the lab expanded scDamID into the epigenetic space. They first combined it with a transcriptional readout.  Later-on they developed EpiDamID, a method to target a diverse set of chromatin types by taking advantage of the binding specificities of single-chain variable fragment antibodies, engineered chromatin reader domains, and endogenous chromatin-binding proteins.   References Kind, J., Pagie, L.,

In this episode of the Epigenetics Podcast, we caught up with Charlotte Proudhon from the Institut Curie to talk about her work on circulating tumor DNA and circulating Epi-mutations as biomarkers in cancer. Charlotte Proudhon started out her research career by investigating circulating tumor DNA (ctDNA). This kind of DNA is shed into the bloodstream by apoptotic tumor cells and can be analyzed after collection by a simple blood draw, which makes it a very useful biomarker for cancer. Using this approach cancers can be identified by their unique mutational fingerprint. However, soon the limitations of this approach became apparent and the fact that this ctDNA is actually shed into the bloodstream as nucleosomal particles was utilized by the Proudhon team and now the methylation fingerprint of the LINE-1 repeats is used as a biomarker for cancer diagnosis and monitoring of the success of a cancer treatment.   References Decraene, C., Silveira, A. B., Bidard, F. C., Vallée, A., Michel, M., Melaabi, S., Vincent

In this episode of the Epigenetics Podcast, we caught up with Luciano Di Croce from the Center of Genomic Regulation in Barcelona to talk about his work on epigenetic landscapes in cancer. The Di Croce Lab focuses on the Polycomb Complex and its influence on diseases like cancer. Luciano Di Croce started out his research career investigating the oncogenic transcription factor PML-RAR. They could show that in leukemic cells knockdown of SUZ12, a key component of Polycomb repressive complex 2 (PRC2), reverts not only histone modification but also induces DNA de-methylation of PML-RAR target genes. More recently the team focused on two other Polycomb related proteins Zrf1 and PHF19 and were able to characterize some of their functions in gene targeting in different disease and developmental contexts.   References Di Croce, L., Raker, V. A., Corsaro, M., Fazi, F., Fanelli, M., Faretta, M., Fuks, F., Lo Coco, F., Kouzarides, T., Nervi, C., Minucci, S., & Pelicci, P. G. (2002). Methyltransferase recruitment a

In this episode of the Epigenetics Podcast, we caught up with Ines Drinnenberg from Institute Curie to talk about her work on the formation of CenH3-deficient kinetochores. The laboratory of Ines Drinneberg focuses on centromeres and how different strategies of centromere organization have evolved in different organisms. While most eukaryotes have monocentric chromosomes, where spindle attachment is restricted to a single chromosomal region resembling such classic X-shape like structures under the microscope, many lineages have evolved holocentric chromosomes where spindle microtubules attach along the entire length of the chromosome. The team was able to show the independent loss of CENH3/CENP-A in holocentric insects. Furthermore, the team focuses on how CenH3-deficient kinetochores form and were able to identify several conserved kinetochore components that emerged as a key component for CenH3-deficient kinetochore formation in Lepidoptera.   References Drinnenberg, I. A., deYoung, D., Henikoff, S., &

In this episode of the Epigenetics Podcast, we caught up with Paul Shiels from the University of Glasgow to talk about his work on the effects of environmental cues on the epigenome and longevity. Paul Shiels and his team focus on the question on how age related health is influenced by the environment. Factors like the socio-economic position, nutrition, lifestyle and the environment can influence the microbiome and the inflammation burden on the body which in turn can alter individual trajectories of ageing and health. The lab also tries to understand the epigenetic, molecular and cellular mechanisms that link the exposome to chronic age related diseases of older people. They have shown that (1)  imbalanced nutrition is associated with a microbiota-mediated accelerated ageing in the general population, (2) a significantly higher abundance of circulatory pathogenic bacteria is found in the most biologically aged, while those less biologically aged possess more circulatory salutogenic bacteria with a capacity

In this episode of the Epigenetics Podcast, we caught up with Sarah Kimmins from Université de Montreal to talk about her work on the epigenetics of human sperm cells. The focus of Sarah Kimmins and her lab is how sperm and offspring health is impacted by the father's environment. The core of this is the sperm epigenome, which has been implicated in complex diseases such as infertility, cancer, diabetes, schizophrenia and autism. The Kimmins lab is interested which players play a role in this and came across the Histone post-translational modification H3K4me3. In this interview we talk about how the father's life choices can impact offspring health, which can also be inherited transgenerationally and how this can be used to develop intervention strategies to improve child and adult health.   References Siklenka, K., Erkek, S., Godmann, M., Lambrot, R., McGraw, S., Lafleur, C., Cohen, T., Xia, J., Suderman, M., Hallett, M., Trasler, J., Peters, A. H., & Kimmins, S. (2015). Disruption of histone methylatio