In this episode of the Epigenetics Podcast, we caught up with Leonid Mirny, Ph.D., from MIT to talk about his work on biophysical modeling of the 3-D structure of chromatin.
Leonid Mirny was part of the initial Hi-C paper titled "Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome" that was published in 2009 in the journal Science. Since then, technology has evolved and Dr. Mirny's group has developed a method called Micro-C that improves the Hi-C protocol by using MNase digestion to increase the resolution to nucleosomal level. This led to the visualization of interactions that were already predicted by his previous biophysical models.
Furthermore, Leonid Mirny worked on finding the mechanism by which chromatin loops are formed. He and his team proposed that loop extrusion underlies TAD formation. In this process, factors like cohesin and CTCF form progressively larger loops but stall at TAD boundaries due to interactions of CTCF with TAD boundaries. He used polymer simulations to show that this model produces TADs and finer-scale features of Hi-C data. Each TAD emerges from multiple loops dynamically formed through extrusion, contrary to typical illustrations of single static loops.
In this interview, we chatted with Dr. Mirny about the details of Hi-C, the development of Micro-C and how it compares to Hi-C, and how biophysical modeling helps to unravel the mechanisms behind loop extrusion.
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Nutriepigenetics: The Effects of Diet on Behavior (Monica Dus)
Investigating the Dynamics of Epigenetic Plasticity in Cancer with Single Cell Technologies (Céline Vallot)
Epigenetic Regulation of Stem Cell Self-Renewal and Differentiation (Margaret “Peggy” Goodell)
Genome-Wide Investigation of Epigenetic Marks and Nucleosome Positioning (Keji Zhao)
The Role of lncRNAs in Tumor Growth and Treatment (Sarah Diermeier)
Unraveling Mechanisms of Chromosome Formation (Job Dekker)
Transcription and Polycomb in Inheritance and Disease (Danny Reinberg)
The Epigenetics of COVID-19
Epigenetic Reprogramming During Mammalian Development (Wolf Reik)
In vivo Nucleosome Structure and Dynamics (Srinivas Ramachandran)
Pioneer Transcription Factors and Their Influence on Chromatin Structure (Ken Zaret)
The Role of Small RNAs in Transgenerational Inheritance in C. elegans (Oded Rechavi)
Development of Site-Specific ChIP Technologies (Hodaka Fujii)
Regulation of Chromatin Organization by Histone Chaperones (Geneviève Almouzni)
How the "Fragile Nucleosome" Science Community Came to Life (Christine Cucinotta, Melvin Noe Gonzalez)
Epigenetic Influence on Memory Formation and Inheritance (Isabelle Mansuy)
Influence of Dynamic RNA Methylation on Gene Expression (Chuan He)
How to Publish in Nature: Lessons from the ENCODE Consortium (Michelle Trenkmann, Senior Editor at Nature)
The Role of Non-Histone Proteins in Chromosome Structure and Function During Mitosis (Bill Earnshaw)
Effects of DNA Methylation on Chromatin Structure and Transcription (Dirk Schübeler)
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