Chromatin architecture & Cardiac epigenetics
The genome is folded into a 3-dimensional conformation in the tight nuclear space. In this project, we are working to unravel how the cardiac epigenome regulates development and disease by exploring chromatin folding dynamics. For these, we have been making use of 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 & knock-in cell lines, and base editing with CRISPR-Cas9.
A desired outcome from this effort is comprehensive maps of the epigenomic changes in cardiac development and disease. We seek to understand how distal regulatory elements are responsible for modulating gene expression through chromatin looping, and whether new heart failure therapies may be developed by targeting the epigenome or chromatin interactions.
Dissecting Chromatin Architecture for Novel Cardiovascular Disease Targets. Circulation, 2019.
Matias, George, Mick, Wilson, Michelle, Lee, Ah Jung