Active Motif's Podcast

In this episode of the Epigenetics Podcast, we caught up with Manel Esteller, Director of the Josep Carreras Leukemia Research Institute to talk about his work on Epigenetics and Epitranscriptomics in Cancer. The focus of Manel Esteller's research career and the focus of his current team is to characterize the epigenome and epitranscriptome of cancer cells in comparison to healthy cells, and their interplay. Ultimately, their goal is to use this knowledge to develop new therapies for cancer. Key achievements from the Esteller lab began with the discovery of the first miRNA that undergoes specific cancer-methylation associated silencing. The team further identified many more miRNAs that also play a role in cancer. Next to miRNAs, Manel Esteller studied the influence of lncRNAs, enhancers and DNA methylation on cancer development and progression, insights that may be used to develop cancer biomarkers and potential treatments.     References Guil, S., Soler, M., Portela, A., Carrère, J., Fonalleras, E., Góm

In this episode of the Epigenetics Podcast, we caught up with Yad Ghavi-Helm from the Institut de Génomique Functionnelle de Lyon to talk about her work on enhancer-promoter interactions during development. The Laboratory of Yad Ghavi-Helm focuses on how developmental genes are regulated by enhancers. Their work shows that developmental genes are often regulated by more than one enhancer and that those enhancers can often be located many kilobases away on the linear chromosome. Furthermore, their research also indicates that the interactions between promoters and their respective enhancers are usually established before the expression of the target gene is switched on, and that those interactions are generally stable during embryogenesis. In addition, those stable interactions seem to coincide with paused RNA Pol II being located at those promoters before gene activation. References Ghavi-Helm, Y., Michaut, M., Acker, J., Aude, J.-C., Thuriaux, P., Werner, M., & Soutourina, J. (2008). Genome-wide lo

In this episode of the Epigenetics Podcast, we caught up with Folami Ideraabdullah from the University of Chapel Hill to talk about her work on the environmental modulation of the epigenome during development. The lab of Folami Ideraabdullah focuses on studying how environmental factors modulate the epigenome. In particular the team investigates how Vitamin D levels influence epigenetic processes and, hence, the susceptibility for diseases like adipositas. Folami Ideraabdullah started with a genome-wide screen of DNA Methylation patterns that are observed after Vitamin D depletion. This work was then followed up by investigating the impact of Vitamin D depletion on mouse sperm DNA methylation.   References Xue, J., Schoenrock, S. A., Valdar, W., Tarantino, L. M., & Ideraabdullah, F. Y. (2016). Maternal vitamin D depletion alters DNA methylation at imprinted loci in multiple generations. Clinical Epigenetics, 8(1), 107. https://doi.org/10.1186/s13148-016-0276-4 Xue, J., Gharaibeh, R. Z., Pietryk,

In this episode of the Epigenetics Podcast, we caught up with Jane Mellor from the University of Oxford to talk about her work on H3K4me3, SET proteins, Isw1 and their role in transcription. Since the beginning of the century, Jane Mellor and her team have focused on H3K4 trimethylation and the factors that influence this mark. They discovered that H3K4me3 is an almost universal mark of the first nucleosome in every transcribed unit and all organisms. She could subsequently, together with the Kouzarides lab, identify SetD1, the enzyme that is responsible for writing this modification. Later on, the team characterized Isw1, a chromatin remodeler which “reads” H3K4me3. More recently the lab focuses on how the polymerase transcribes throughout the first nucleosomes of the transcribed region at the +2 nucleosome, with the help of Spt4.   References Santos-Rosa, H., Schneider, R., Bannister, A. J., Sherriff, J., Bernstein, B. E., Emre, N. C. T., Schreiber, S. L., Mellor, J., & Kouzarides, T. (2002). Activ

In this episode of the Epigenetics Podcast, we caught up with Katja Kobow from the Universitätsklinikum Erlangen to talk about her work on the role of DNA methylation in Epilepsy. Katja Kobow started studying the role of Epigenetics in Epilepsy by doing a genome wide Bisulfite-Sequencing screen that revealed a typical DNA methylation signature of epileptic patients versus healthy controls. After these initial results in human patient samples, she switched to an animal model to investigate this further. Now the focus of the Kobow Lab is to look for the same DNA methylation signature in blood samples, using this as a basis for the development of a potential prognostic marker for Epilepsy.   References Jablonski, Janos, Lucas Hoffmann, Ingmar Blümcke, Anna Fejtová, Steffen Uebe, Arif B. Ekici, Vadym Gnatkovsky, and Katja Kobow. 2021. “Experimental Epileptogenesis in a Cell Culture Model of Primary Neurons from Rat Brain: A Temporal Multi-Scale Study.” Cells 10(11):3004. doi: 10.3390/cells10113004. Jablo

In this episode of the Epigenetics Podcast, we caught up with Emily Bernstein from Icahn Schoon of Medicine at Mount Sinai to talk about her work on MacroH2A function and the role of Polycomb proteins in its epigenetic regulation, and how this affects in stem cell development and disease. The Bernstein Lab focuses on histone variants, in particular the variants of macroH2A. Chromatin architecture is influenced by the composition of the nucleosome and, hence, exchanging the core histones for histone variants can have a major impact on chromatin structure. MacroH2A is the histone with the most variants, due to a 30kDa non-histone domain (macro domain) at their C-termini. This variation leads to many macroH2A variants, which have been found to have regulatory roles in the cell. Among other things the Bernstein Lab has shown that macroH2A is enriched at a critical set of Utx target genes whose expression is critical for the early stages of induced pluripotency.   References Kapoor, A., Goldberg, M. S., Cumbe

In this episode of the Epigenetics Podcast, we caught up with Jane Skok from New York University School of Medicine to talk about her work on spatio-temporal alterations in chromosome dynamics. Studies demonstrating that nuclear organization and long-range chromatin interactions play essential roles in gene regulation have been the focus of the Skok Lab, where the team has played a leading role. Their initial studies focused on lymphocyte development and the control of V(D)J recombination, a key part of generating the diverse repertoire of B-cell antibodies and T-cell receptors. The Skok Lab was among the first to demonstrate the possibility of chromatin forming dynamic loops which lead to the formation of reversible intra-locus loops in the immunoglobulin and T-cell receptor loci and to a profound impact on the ability of B and T cells to generate receptor diversity.   References Roldán, E., Fuxa, M., Chong, W., Martinez, D., Novatchkova, M., Busslinger, M., & Skok, J. A. (2005). Locus “decontracti

In this episode of the Epigenetics Podcast, we caught up with Marieke Oudelaar from the Max Planck Institute for Biophysical Chemistry to talk about her work on chromatin organization during development and disease. Marieke Oudelaar and her team focus on on developing high-resolution Chromosome Conformation Capture (3C) based techniques, like low-input Capture-C, Tri-C, and Tiled-C. Those techniques are then used in combination with other genomic techniques, genetic perturbations, and computational approaches to investigate the 3D structure of chromatin in development and disease. The team focused on the interplay between genome organisation and regulation during mammalian differentiation, and how perturbations in these processes contribute to human disease, including cancer.   References Oudelaar, A. M., Davies, J. O. J., Downes, D. J., Higgs, D. R., & Hughes, J. R. (2017). Robust detection of chromosomal interactions from small numbers of cells using low-input Capture-C. Nucleic Acids Research, 45

In this episode of the Epigenetics Podcast, we caught up with Camila dos Santos from Cold Spring Harbor Laboratories to talk about her work on enhancers and chromatin remodeling in mammary gland development. The lab of Camila dos Santos focuses on epigenetic regulation of normal and malignant mammary gland development. After puberty, the next significant phase in mammary gland development occurs in pregnancy, including changes in cellular function, and tissue reorganization. A different and as significant change in mammary glands occurs in the development breast cancer. Camila dos Santos and her lab were recently able to show that the reaction of mammary glands to a second pregnancy is different than to a first one, which is accompanied by changes in the DNA methylome of the cells. Furthermore, the lab studies the connection of pregnancy-induced epigenetic changes of chromatin and the risk of cancer development.   References dos Santos, C. O., Rebbeck, C., Rozhkova, E., Valentine, A., Samuels, A., Kadi

In this episode of the Epigenetics Podcast, we caught up with Marnie Blewitt from the Walter and Eliza Hall Institute of Medical Research to talk about her work on the role of SMCHD1 in Development and Disease. The Laboratory of Marnie Blewitt focuses finding inhibitors or activators for the epigenetic regulator SMCHD1. Marnie Blewitt identified and characterized this protein during her PhD and the findings were published in 2008 in Nature Genetics. Since then, she and her team were able to investigate the function of this protein further. By doing so, they showed the involvement of SMCHD1 in cancer and several other diseases. Currently the lab is screening for small molecules that can act as inhibitors or activators of SMCHD1 the former as potential treatments for facioscapulohumeral muscular dystrophy, the latter for Prader Willi and Schaaf-Yang syndromes, both of which have no current targeted treatments.   References Blewitt, M. E., Gendrel, A.-V., Pang, Z., Sparrow, D. B., Whitelaw, N., Craig, J. M

In this episode of the Epigenetics Podcast, we caught up with Efrat Shema from the Weizmann Institute of Science to talk about her work on Single Molecule Imaging of chromatin, and the analysis of nucleosomes circulating in plasma. In ChIP-Seq experiments the peak you get as a read out represents an average over, most often, millions of cells. Furthermore, one often does not know if that peak represents one or more than one nucleosome. If you then want to study multiple marks at the same time, the question remains: do those modifications occur at the same time, in the same cell? The Laboratory of Efrat Shema works on answering those questions by developing methods to study the modification patterns on single nucleosomes with single molecule imaging. With that it is possible to study single nucleosomes in a high throughout manner to identify the modifications they are decorated with. A subsequent sequencing step makes it possible to identify the genomic location of that nucleosome.   References Shema, E

In this episode of the Epigenetics Podcast, we caught up with Serena Sanulli from Stanford University to talk about her work on Heterochromatin Protein 1 (HP1), the structure of chromatin on the atomic-scale and the meso-scale, and phase separation. The Laboratory of Serena Sanulli is interested in finding connections between changes that happen on the nucleosomal level and the resulting impact on chromatin conformation on the meso-scale. They combine methods like NMR and Hydrogen-Deuterium Exchange-MS with Cell Biology and Genetics. This enables them to dissect how cells use the diverse biophysical properties of chromatin to regulate gene expression across length and time scales. A second focus of the lab is HP1, which interacts with the nucleosome and changes its conformation, enabling the compaction of the genome into heterochromatin, effectively silencing genes in that region. A high concentration of HP1 leads to the phenomenon of phase separation in the nucleus, which the Sanulli lab is now investiga

In this episode of the Epigenetics Podcast, we caught up with Catherine Jensen Peña from Princeton University to talk about her work on early life stress and its effects on behavior. The Laboratory of Catherine Peña focuses on how early life experiences are encoded and maintained into adulthood, with a long-lasting impact on behavior. Recent work showed, that child maltreatment and other forms of early life stress increase the lifetime risk of depression and other mood, anxiety, and drug disorders by 2-4 fold. The Peña Lab uses genome wide approaches to investigate key brain regions with a two-hit stress model. Using RNA-Seq, the Peña Lab has shown that depression-like gene expression patterns are programmed by early life stress, similar to observations in mice exhibiting depression-like behavior after adult stress and are visible even before behavioral changes. Furthermore, latent and unique transcriptional responses to adult stress among a subset of genes is programmed by early life stress. The role of

In this episode of the Epigenetics Podcast, we caught up with Ali Shilatifard from Northwestern University to talk about his work on targeting COMPASS to cure childhood leukemia. The Shilatifard Lab studies childhood leukemia and how it can potentially be treated using epigenetic targets. The team focuses on is SET1/COMPASS, a histone H3 lysine4 methylase. Ali Shilatifard was able to purify and identify its activity, with results published in 2001 in PNAS. This protein complex is conserved from yeast to drosophila to humans. Surprisingly, the Shilatifard Team could show that the catalytic activity of COMPASS is not necessary for viability of drosophila. Furthermore, they found that catalytic activity was not the decisive feature of the complex, but rather its role in the context of chromatin structure, in particular a protein domain that only spans 80 amino acids within the 4000 amino acid protein.   References Miller, T., Krogan, N. J., Dover, J., Erdjument-Bromage, H., Tempst, P., Johnston, M., Gre

In this episode of the Epigenetics Podcast, we caught up with Yael David from Memorial Sloan Kettering Cancer Center in New York to talk about her work on Effects of Non-Enzymatic Covalent Histone Modifications on Chromatin.  The David lab studies on non-enzymatic covalent modifications of Histones, including Histone glycation and citrullination. These modifications recognize metabolites that are produced in the cell and aid as a sensor for chromatin to quickly adapt to cellular changes. These unique modifications do not have a so-called erasing enzyme, which makes them terminal, rendering these sites inaccessible for further modifications such as methylation or acetylation.   A second area of research in the David lab is Histone H1. The lab has developed a new method to purify Histone H1, superior to the commonly used method of acid extraction which leads to degradation of Histone H1. This purification method enabled the lab to purify and characterize the functional properties of all Histone H1 variants.

In this episode of the Epigenetics Podcast, we caught up with Jason Buenrostro from Harvard University to talk about his work on developing biological tools to measure chromatin dynamics in single-cells. He explains how his lab uses these tools to study chromatin alterations in different cell types and disease states to uncover new mechanisms of gene regulation and their contribution to those diseases. In his first years of his research career Jason Buenrostro took a risk and just added an enzyme called Transposase to cells in a cell culture. What he saw on a subsequent agarose gel astonished him. He was able to recreate a nucleosomal ladder that he knew from experiments using MNase or DNase-Seq, however, without the tedious steps of optimization. In the following years he optimized that method and data analyzation into a method known today as ATAC-Seq. In recent years he was also able to bring ATAC-Seq to the next level and developed single cell ATAC-Seq (scATAC-Seq), and combining it with RNA-Seq in a mul

In this episode of the Epigenetics Podcast, we caught up with Karmella Haynes from Emory University to talk about her work on synthetic chromatin epigenetics. The Haynes lab focuses on the design of synthetic chromatin sensor proteins. The first one of this kind, the Polycomb Transcription Factor (PcTF), was published in 2011. It senses H3K27me3 and recruits effector proteins to the sites of this modification. This sensor can be brought into cancer cells to activate hundreds of silenced genes. The lab now focuses on characterizing the effects of these sensor proteins genome wide, and seeks to find a way to deliver those sensor into cancer cells, without affecting healthy cells. In this Episode we discuss how Karmella Haynes got into the field of Epigenetics, how she designed the PcTF sensor proteins, and the way she came to learn how important the right control experiments are. In the end we also discuss her activities to promote diversity and inclusion in science.   References Haynes, K. A., & S

In this episode of the Epigenetics Podcast, we caught up with Enrico Glaab from the University of Luxemburg to talk about his work on the development of integrative machine learning tools for neurodegenerative diseases. The work of Dr. Enrico Glaab focuses on neurodegenerative disorders like Parkinson’s and Alzheimer’s disease. In his group his team works on the development of software tools to analyze molecular, clinical and neuroimaging data for those diseases that can be used and applied easily by scientists and deliver publication ready figures. More recently, Enrico Glaab's group got interested in the influence of Epigenetics in Parkinson's and Alzheimer's disease. In this Episode we discuss how Enrico Glaab made the switch from wet-lab to becoming a bioinformatician and how he uses integrative machine learning tools to find approaches to not only cure but also be able to detect neurodegenerative diseases like Alzheimer's or Parkinson's early on.   References Enrico Glaab, Reinhard Schneider (2015)

In this episode of the Epigenetics Podcast, we caught up with Diane Dickel from Lawrence Berkeley National Laboratory to talk about her work on ultraconserved enhancers and enhancer redundancy. Diane Dickel and her co-workers study non-coding regions of the genome that harbor distant-acting transcriptional regulatory regions, called enhancers. Enhancers have been shown to be critical for normal embryonic development, implying evolutional conservation. Diane Dickel and her team try to identify and characterize enhancers at a genomic scale. Their efforts include the use of CRISPR/CAS9 to mutate enhancer sequences in order to understand sequence dependent functional relevance. In this episode we discuss the function of ultraconserved enhancers, what ultraconservation actually means, how enhancer redundancy works and how Diane Dickel dealt with a failed PhD project.   References Dickel, D. E., Ypsilanti, A. R., Pla, R., Zhu, Y., Barozzi, I., Mannion, B. J., Khin, Y. S., Fukuda-Yuzawa, Y., Plajzer-Frick, I.,

In this episode of the Epigenetics Podcast, we caught up with Sandra Hake from the Justus Liebig University in Giessen to talk about her work on variants of core histones and their role as modulators of chromatin structure and function. The overarching goal of Sandra Hake's research group is to understand how changes in chromatin structure and composition can influence various DNA-based processes, such as gene expression, repair of DNA damage, cell cycle progression, and genome stability. Their work deals with the study of histone variants which, together with DNA, represent the building blocks of the smallest chromatin components, the nucleosomes. They also investigate whether mutations and/or post-translational histone modifications and the deregulation of histone variant networks influence the emergence of diseases, especially the emergence of tumors. In this episode we discuss how Sandra Hake approaches the characterization and identification of novel histone variants like H3.3, H3.X and H3.Y, what it's