Epigenetics Podcast

Nutriepigenetics: The Effects of Diet on Behavior (Monica Dus)

In this episode of the Epigenetics Podcast, we caught up with Monica Dus from the University of Michigan to talk about her work on nutriepigenetics and the effects of diet on behavior.
The focus of Monica Dus and her team is to study the effect of sugar on the brain and how diet has an effect on behavior. The Dus lab takes a multidisciplinary approach to answer questions like "What causes animals to overeat if they consume foods rich in sugar, salt, and fat?" and "How does such a diet alter the basic physiology and biochemistry of the brain to promote food intake and weight gain?" By doing this, they showed recently that the Polycomb Repressive Complex 2 (PRC2) plays a role in reprogramming the sensory neurons of Drosophila Melanogaster, reducing sweet sensation and hence promoting obesity when flies are fed a high sugar diet. In response to that diet the binding of PRC2 to chromatin in sweet gustatory neurons is altered and reshapes the developmental transcriptional network.
In this episode we discuss how flies taste food and sugar, how sugar modulates taste, and how a high sugar diet influences the taste and amount of food flies eat.
 
References
Monica Dus, SooHong Min, … Greg S. B. Suh (2011) Taste-independent detection of the caloric content of sugar in Drosophila (Proceedings of the National Academy of Sciences of the United States of America) DOI: 10.1073/pnas.1017096108
Christina E. May, Anoumid Vaziri, … Monica Dus (2019) High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster (Cell Reports) DOI: 10.1016/j.celrep.2019.04.027
Daniel Wilinski, Jasmine Winzeler, … Monica Dus (2019) Rapid metabolic shifts occur during the transition between hunger and satiety in Drosophila melanogaster (Nature Communications) DOI: 10.1038/s41467-019-11933-z
Anoumid Vaziri, Morteza Khabiri, … Monica Dus (2020) Persistent epigenetic reprogramming of sweet taste by diet (Science Advances) DOI: 10.1126/sciadv.abc8492
How to Science Podcast
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Related Episodes
Transcription and Polycomb in Inheritance and Disease (Danny Reinberg)
The Role of Small RNAs in Transgenerational Inheritance in C. elegans (Oded Rechavi)
Epigenetic Origins Of Heterogeneity And Disease (Andrew Pospisilik)
 
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Investigating the Dynamics of Epigenetic Plasticity in Cancer with Single Cell Technologies (Céline Vallot)

In this episode of the Epigenetics Podcast, we caught up with Céline Vallot from L'Institut Curie in Paris to discuss her work on investigating the dynamics of epigenetic plasticity in cancer with single cell technologies.
During her Post-Doc years Céline Vallot worked on the inactive X chromosome. Using RNA-Seq she discovered a novel long noncoding RNA (lncRNA) called XACT. This lncRNA is expressed from and coats the active X chromosome in human pluripotent cells. Céline Vallot also showed that XACT is specific to humans and cannot be found in mice.
After starting her own lab, Céline Vallot began to focus on Single Cell Epigenomics in Cancer. She and her team developed a high-throughput single-cell ChIP-seq approach which relies on a droplet microfluidics platform to profile the chromatin landscape of thousands of cells. By doing so they could show that a subset of cells within untreated drug-sensitive tumors share a common chromatin signature. This would have been impossible with common bulk approaches. These cells are characterized by the loss of H3K27me3, which leads to stable transcriptional repression, influencing genes that are known to promote resistance to treatment.
In this episode we discuss how Céline Vallot had her once-in-a-lifetime scientific eureka-moment, when, during her postdoc, she first saw XACT coating the whole X-Chromosome in humans and then how she pivoted when starting her own lab and focuses now on single-cell epigenomics in cancer.
 
References
Céline Vallot, Christophe Huret, … Claire Rougeulle (2013) XACT , a long noncoding transcript coating the active X chromosome in human pluripotent cells (Nature Genetics) DOI: 10.1038/ng.2530
Kevin Grosselin, Adeline Durand, … Annabelle Gérard (2019) High-throughput single-cell ChIP-seq     identifies heterogeneity of chromatin states in breast cancer (Nature Genetics) DOI: 10.1038/s41588-019-0424-9
Pacôme Prompsy, Pia Kirchmeier, … Céline Vallot (2020) Interactive analysis of single-cell epigenomic landscapes with ChromSCape (Nature Communications) DOI: 10.1038/s41467-020-19542-x
Justine Marsolier, Pacôme Prompsy, … Céline Vallot (2021) H3K27me3 is a determinant of chemotolerance in triple-negative breast cancer (bioRxiv) DOI: 10.1101/2021.01.04.423386
 
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Dosage Compensation in Drosophila (Asifa Akhtar)
Epigenetics and X-Inactivation (Edith Heard)
Cancer and Epigenetics (David Jones)
 
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Epigenetic Regulation of Stem Cell Self-Renewal and Differentiation (Margaret “Peggy” Goodell)

In this episode of the Epigenetics Podcast, we caught up with Margaret (“Peggy”) Goodell from Baylor College of Medicine in Houston, Texas to talk about her work on the epigenetic regulation of stem cell self-renewal and differentiation.
Dr. Margret Goodell's laboratory focuses on how differentiation and self-renewal is regulated in hematopoietic stem cells (HSC). In the early stages of her research career, however, Dr. Goodell was able to develop a new method to purify stem cells. This method was based on the characteristic of stem cells to pump out the Hoechst dye that was used for the purification.
In recent years, the focus of the lab has been to identify how HSCs decide whether to self-renew or differentiate. To get an answer to this question, the lab has performed genome-wide screens to find differentially expressed genes during the decision process. By doing that, they recently found that the DNA methyltransferase 3A (DNMT3A) was highly and specifically expressed in HSCs and that it is required for differentiation. When DNMT3A was knocked out in HSCs, the cell population expanded dramatically and the ability to differentiate was impaired. This finding led to further experiments in this area and to the discovery of so-called DNA methylation canyons in the genome, which are large regions of very low DNA methylation that harbor highly conserved regulator genes.
In this episode we discuss how Dr. Peggy Goodell described a new approach to isolate hematopoietic stem cells even though she was not looking for that, how she discovered DNMT3A as an important factor in stem cell decision making, and how she entered and approached new fields of research along the path of her research career. 
 
References
M. A. Goodell, K. Brose, … R. C. Mulligan (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo (The Journal of Experimental Medicine) DOI: 10.1084/jem.183.4.1797
Shannon McKinney-Freeman, Margaret A. Goodell (2004) Circulating hematopoietic stem cells do not efficiently home to bone marrow during homeostasis (Experimental Hematology) DOI: 10.1016/j.exphem.2004.06.010
Stuart M. Chambers, Chad A. Shaw, … Margaret A. Goodell (2007) Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation (PLoS biology) DOI: 10.1371/journal.pbio.0050201
Grant A. Challen, Deqiang Sun, … Margaret A. Goodell (2011) Dnmt3a is essential for hematopoietic stem cell differentiation (Nature Genetics) DOI: 10.1038/ng.1009
 
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Epigenetic Reprogramming During Mammalian Development (Wolf Reik)
Effects of DNA Methylation on Chromatin Structure and Transcription (Dirk Schübeler)
CpG Islands, DNA Methylation, and Disease (Sir Adrian Bird)
 
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Genome-Wide Investigation of Epigenetic Marks and Nucleosome Positioning (Keji Zhao)

In this episode of the Epigenetics Podcast, we caught up with Dr. Keji Zhao from the National Heart, Lung, and Blood Institute at the National Institutes of Health in Bethesda, MD, to talk about his work on the genome-wide investigation of epigenetic marks and nucleosome positioning.
Dr. Keji Zhao pioneered in the development of cutting-edge techniques in the field of epigenetics. Current methods at that time relied on DNA microarrays, however, Dr. Zhao wanted a more comprehensive and unbiased approach that would avoid the shortfalls of these array-based methods. Hence, he set out to develop new sequencing-based methods like ChIP-Seq and MNase-Seq with accompanying computational methods to analyze the huge amount of sequencing data that would be generated.
Using the above-mentioned techniques, Dr. Zhao was able to show that histone deacetylases (HDACs) and histone acetyltransferases (HATs) were found at inactive and active genes, respectively, as previously thought. Surprisingly, he was also able to show that HDACs were also located at active genes. Furthermore, both, HATs and HDACs can be found at low levels at silenced genes.
In this episode we discuss the story behind how Dr. Keji Zhao was one of the pioneers of the chromatin immunoprecipitation technology, how he discovered the genomic locations of HATs and HDACs, and in the end he shares some tips and tricks on how to get the best results in ChIP-Seq assays.
 
References
Artem Barski, Suresh Cuddapah, … Keji Zhao (2007) High-resolution profiling of histone methylations in the human genome (Cell) DOI: 10.1016/j.cell.2007.05.009
Dustin E. Schones, Kairong Cui, … Keji Zhao (2008) Dynamic regulation of nucleosome positioning in the human genome (Cell) DOI: 10.1016/j.cell.2008.02.022
Zhibin Wang, Chongzhi Zang, … Keji Zhao (2009) Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes (Cell) DOI: 10.1016/j.cell.2009.06.049
Wenfei Jin, Qingsong Tang, … Keji Zhao (2015) Genome-wide detection of DNase I hypersensitive sites in single cells and FFPE tissue samples (Nature) DOI: 10.1038/nature15740
Binbin Lai, Weiwu Gao, … Keji Zhao (2018) Principles of nucleosome organization revealed by single-cell micrococcal nuclease sequencing (Nature) DOI: 10.1038/s41586-018-0567-3
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In Vivo Nucleosome Structure and Dynamics (Srinivas Ramachandran)
Development of Site-Specific ChIP Technologies (Hodaka Fujii)
Multiple Challenges in ChIP (Adam Blattler)
 
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The Role of lncRNAs in Tumor Growth and Treatment (Sarah Diermeier)

In this episode of the Epigenetics Podcast, we caught up with Dr. Sarah Diermeier from the University of Otago in New Zealand to talk about her work on the role of long non-coding RNAs in tumor growth and treatment.
Although only 1-2% of the human genome is transcribed into mRNAs that code for proteins, 75% of the genome is transcribed into non-coding RNAs. The function of these non-coding RNAs lie in the regulation of cellular processes and hence, offer the possibility of therapeutic intervention. Dr. Diermeier and her laboratory focus on a subset of these non-coding RNAs: the long non-coding RNAs (lncRNAs) that have been shown to play a role in breast and colorectal cancers.
This interview discusses how the Diermeier lab uses state-of-the-art techniques to both answer fundamental questions about biological mechanisms and also for translational research approaches. We also touch upon Dr. Diermeier becoming mother during her first years being a PI and the challenges and opportunities faced while raising a child and running a lab, and how the University of Otago and the State of New Zealand support young mothers in science.
This episode also tells the stories behind how Dr. Sarah Diermeier ended up in New Zealand, how her childhood influenced her career path, the role of lncRNAs in cancer, and how she deals with being a young PI and a mother at the same time.
 
References
R. Gualdi, P. Bossard, … K. S. Zaret (1996) Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control (Genes & Development) DOI: 10.1101/gad.10.13.1670
L. A. Cirillo, C. E. McPherson, … K. S. Zaret (1998) Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome (The EMBO journal) DOI: 10.1093/emboj/17.1.244
Lisa Ann Cirillo, Frank Robert Lin, … Kenneth S. Zaret (2002) Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4 (Molecular Cell) DOI: 10.1016/s1097-2765(02)00459-8 
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Unraveling Mechanisms of Chromosome Formation (Job Dekker)

In this episode of the Epigenetics Podcast, we caught up with Job Dekker from the University of Massachusetts Medical School to talk about his work on unraveling mechanisms of chromosome formation.
In 2002, during graduate school, Job Dekker was the first author on the paper describing the chromosome conformation capture (3C) method, which revolutionized the field of nuclear architecture. In the 3C protocol, chromatin is crosslinked using formaldehyde and then digested using a restriction enzyme. After ligating the digested blunt ends of crosslinked DNA fragments together they can be analyzed using qPCR. In the next couple of years 3C was further developed and methods like 4C, 5C, and Hi-C were published. This led to the generation of genome-wide contact maps which helped understand the 3-D organization of the nucleus.
Job Dekker’s research group is also part of the 4D Nucleome initiative, which is dedicated to understanding the structure of the human genome. More recent work of the lab includes analyzing interactions between and along sister chromatids with a method called SisterC and expanding their research to organisms like dinoflagellates to learn more about the basic organization principles of the genome.
In this episode, we discuss the story behind the idea of the chromosome conformation capture method, how close Job Dekker was to giving up on it, how the 3C methods evolved, the importance of data visualization, and we touch on parts of his current work on dinoflagellates.
 
References
Job Dekker, Karsten Rippe, … Nancy Kleckner (2002) Capturing Chromosome Conformation (Science) DOI: 10.1126/science.1067799
Josée Dostie, Todd A. Richmond, … Job Dekker (2006) Chromosome Conformation Capture Carbon Copy (5C): A massively parallel solution for mapping interactions between genomic elements (Genome Research) DOI: 10.1101/gr.5571506
Erez Lieberman-Aiden, Nynke L. van Berkum, … Job Dekker (2009) Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome (Science) DOI: 10.1126/science.1181369
Amartya Sanyal, Bryan R. Lajoie, … Job Dekker (2012) The long-range interaction landscape of gene promoters (Nature) DOI: 10.1038/nature11279
Marlies E. Oomen, Adam K. Hedger, … Job Dekker (2020) Detecting chromatin interactions between and along sister chromatids with SisterC (Nature Methods) DOI: 10.1038/s41592-020-0930-9 • Job Dekker, Andrew S. Belmont, … 4D Nucleome Network (2017) The 4D nucleome project (Nature) DOI: 10.1038/nature23884 • The 4D Nucleome Project
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Transcription and Polycomb in Inheritance and Disease (Danny Reinberg)

In this episode of the Epigenetics Podcast, we caught up with Dr. Danny Reinberg from the New York University School of Medicine to talk about his work on transcription and polycomb in inheritance and disease.
Dr. Danny Reinberg is a pioneer in the characterization of transcription factors for human RNA polymerase II. In his groundbreaking work in the 1990s, he purified the essential transcription factors and reconstituted the polymerase in vitro on both naked DNA and chromatin.  Dr. Reinberg next started focusing on the polycomb repressive complex 2 (PRC2), which is the only known methyltransferase for lysine 27 on histone H3. He biochemically characterized the PRC2 subunits EZH1 and EZH2. More recently, Dr. Reinberg has been investigating the role of PRC2 in neurons. 
This interview discusses the story behind how Dr. Danny Reinberg started his research career by identifying the essential RNA polymerase transcription factors, how he discovered and characterized the polycomb repressive complex 2 (PRC2), and what his research holds for the future.
 
References
H. Lu, L. Zawel, … D. Reinberg (1992) Human general transcription factor IIH phosphorylates the C-terminal domain of RNA polymerase II (Nature) DOI: 10.1038/358641a0
A. Merino, K. R. Madden, … D. Reinberg (1993) DNA topoisomerase I is involved in both repression and activation of transcription (Nature) DOI: 10.1038/365227a0
G. Orphanides, W. H. Wu, … D. Reinberg (1999) The chromatin-specific transcription elongation factor FACT comprises human SPT16 and SSRP1 proteins (Nature) DOI: 10.1038/22350
Andrei Kuzmichev, Kenichi Nishioka, … Danny Reinberg (2002) Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein (Genes & Development) DOI: 10.1101/gad.1035902
Andrei Kuzmichev, Raphael Margueron, … Danny Reinberg (2005) Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation (Proceedings of the National Academy of Sciences of the United States of America) DOI: 10.1073/pnas.0409875102
Ozgur Oksuz, Varun Narendra, … Danny Reinberg (2018) Capturing the Onset of PRC2-Mediated Repressive Domain Formation (Molecular Cell) DOI: 10.1016/j.molcel.2018.05.023
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The Epigenetics of COVID-19

In this episode of the Epigenetics Podcast, we caught up with Dr. Sandra Atlante and Dr. Carlo Gaetano from the Instituti Clinici Scientifici Maugeri in Pavia, Italy, to talk about the roles epigenetic mechanisms play in COVID-19.
In early 2020 a novel coronavirus, SARS-CoV-2, emerged in Wuhan, China. This coronavirus causes the coronavirus disease 2019 (COVID-19) and rapidly spread all over the globe. In a worldwide effort, scientists and doctors tried to find drugs and looked for vaccines to help contain the spreading of the virus. It seems that an overreaction of the immune system, the so called "cytokine storm," could be one of the major complications of this disease. This reaction is not directly linked to the viral infection but is an overreaction of the body's own immune system. Therefore, small molecules that regulate gene expression via chromatin modifying enzymes might help keep the immune system in check.
In this episode we discuss how Dr. Gaetano and Dr. Atlante set up studies to investigate the epigenetic response to a SARS-CoV-2 infection, which epigenetic factors play a role in disease progression, and what we can expect from mutations of the virus in the future.
 
References
Sandra Atlante, Alessia Mongelli, … Carlo Gaetano (2020) The epigenetic implication in coronavirus infection and therapy (Clinical Epigenetics) DOI: 10.1186/s13148-020-00946-x
 
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