Abstract 331: Genome-wide Analysis of Cardiac and Cardiac Fibroblasts Regulatory Elements Reveals Combinatorial Control of Gene Expression

• Published in: Circulation research Vol. 121; no. suppl_1
• Main Authors: Golan Lagziel, Tal, Caspi, Lilac, Lewis, Yair, Kehat, Izhak
• Format: Journal Article
• Language: English
• Published: 21.07.2017
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/res.121.suppl_1.331

Abstract only The mammalian body contains several hundred cell types that share the same genome, but can express distinct gene signatures. This specification of gene expression is achieved through the activity of cis-regulatory genomic elements (CRE), such as enhancers, promoters, and silencers. The Assay for Transposase-Accessible Chromatin followed by sequencing (ATAC-seq) can identify nucleosome evicted open chromatin, an established marker of regulatory regions. Using a differential ATAC-seq approach, coupled with RNA-seq, H3K27ac ChiP-seq, and computational transcription factor (TFs) binding analysis we comprehensively mapped cell-type and condition specific cis regulatory elements for cardiac fibroblasts and cardiomyocytes, and outlined the TFs that control them. We show that in cardiomyocytes six main transcription factor groups, that control their own and each other’s expression, cooperatively bind discrete distal enhancers that are located at a variable distance from the transcription start site of their target genes. None of these factors is entirely tissue specific in expression, yet various combination of binding sites for these factors, densely clustered within a nucleosome length of genomic stretch make these CREs tissue specific. Multiple tissue specific CREs in turn, are clustered around highly tissue specific genes, and multiple factors, acting from the same and from different CREs can converge on these genes to control their tissue specific expression. Together our data puts forward a mechanistic multi-level combinatorial model for cardiac specific genes expression