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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The role of DNA Methylation in Epilepsy (Katja Kobow)
MacroH2A Function in Development and Disease (Emily Bernstein)
Spatio-Temporal Alterations in Chromosome Dynamics (Jane Skok)
Chromatin Organization During Development and Disease (Marieke Oudelaar)
Enhancers and Chromatin Remodeling in Mammary Gland Development (Camila dos Santos)
The Role of SMCHD1 in Development and Disease (Marnie Blewitt)
Single-Molecule Imaging of the Epigenome (Efrat Shema)
Heterochromatin Protein 1 and its Influence on the Structure of Chromatin (Serena Sanulli)
The Effects of Early Life Stress on Mammalian Development (Catherine J. Peña)
Targeting COMPASS to Cure Childhood Leukemia (Ali Shilatifard)
Effects of Non-Enzymatic Covalent Histone Modifications on Chromatin (Yael David)
ATAC-Seq, scATAC-Seq and Chromatin Dynamics in Single-Cells (Jason Buenrostro)
Synthetic Chromatin Epigenetics (Karmella Haynes)
Development of Integrative Machine Learning Tools for Neurodegenerative Diseases (Enrico Glaab)
Ultraconserved Enhancers and Enhancer Redundancy (Diane Dickel)
Variants of Core Histones: Modulators of Chromatin Structure and Function (Sandra Hake)
DNA Methylation and Mammalian Development (Déborah Bourc'his)
Chromatin Analysis using Mass Spectrometry (Axel Imhof)
Chromatin Profiling: From ChIP to CUT&RUN, CUT&Tag and CUTAC (Steven Henikoff)
Effects of DNA Methylation on Diabetes (Charlotte Ling)
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