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 Impact of Sequence Variation on Transcription Factor Binding (Sven Heinz)
Comparing CUT&Tag to ENCODE ChIP-Seq in Alzheimer's Disease Samples (Sarah Marzi)
The Role of Hat1p in Chromatin Assembly (Mark Parthun)
The Impact of Paternal Diet on Offspring Metabolism (Upasna Sharma)
H3K36me3, H4K16ac and Cryptic Transcription in Ageing (Weiwei Dang)
Split-Pool Recognition of Interactions by Tag Extension (SPRITE) (Mitch Guttman)
MLL Proteins in Mixed-Lineage Leukemia (Yali Dou)
Sex-biased Imprinting and DNA Regulatory Landscapes During Reprogramming (Sam Buckberry)
BET Proteins and Their Role in Chromosome Folding and Compartmentalization (Kyle Eagen)
Epigenetic Underpinnings of Human Addiction (Francesca Telese & Jessica Zhou)
H3K79 Methylation, DOT1L, and FOXG1 in Neural Development (Tanja Vogel)
Function of Insulators in 3D Genome Folding (Maria Gambetta)
Contribution of the Estrogen Receptor to Breast Cancer Progression (Jason Carroll)
Inheritance of Transcriptional Memory by Mitotic Bookmarking (Sheila Teves)
Differential Methylated Regions in Autism Spectrum Disorders (Janine La Salle)
DNA Damage in Longevity and Ageing (Björn Schumacher)
The Impact of Chromatin Modifiers on Disease Development and Progression (Capucine van Rechem)
Long-Range Transcriptional Control by 3D Chromosome Structure (Luca Giorgetti)
Transgenerational Inheritance and Epigenetic Imprinting in Plants (Mary Gehring)
When is a Peak a Peak? (Claudio Cantù)
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