Chromatin architecture & Epigenetics
The DNA chromatin is folded into xxxxx.
In this project, we have been working to unravel how the epigenome regulates cardiac development and disease by looking at chromatin folding dynamics. For these, we have made use of epigenetic methodologies including ChIP-seq, Reduced representation bisulfite sequencing (RRBS), whole genome bisulfite suequencing (WGBS), Chromosome Conformation Capture (3C, 4C, Hi-C, HiChIP), confocal live imaging with dCas9 -fluorescent fusion proteins, CRISPR-Cas9 mediated knockout & knockin cell lines, and base editing with CRISPR-Cas9.
A potential outcome from this effort is a comprehensive map of the epigenomic changes in cardiac development and disease. We seek to understand how distal regulatory elements may modulate gene expression through chromatin looping, and whether new heart failure therapies may be developed by targeting the epigenome or chromatin.
Disease and phenotype relevant genetic variants identified from histone acetylomes in human hearts. BioRxiv, 2019.
A Robust CTCF-Based Chromatin Architecture Underpins Epigenetic Changes in the Heart Failure Stress-Gene Response. Circulation, 2019.
Single cardiomyocyte nuclear transcriptomes reveal a lincRNA-regulated de-differentiation and cell cycle stress-response in vivo. Nature Communication, 2018.
A Transcriptomic and Epigenomic Comparison of Fetal and Adult Human Cardiac Fibroblasts Reveals Novel Key Transcription Factors in Adult Cardiac Fibroblasts. JACC, 2016.
Matias, George, Mick, Wilson, Michelle, Arnaud
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