Publication

Detailed Regulatory Interaction Map of the Human Heart Facilitates Gene Discovery for Cardiovascular Disease

current
   May 5th, 2023 at 1:50pm

Overview


Abstract

Most disease-associated variants identified by population based genetic studies are non-coding, which compromises finding causative genes and mechanisms. Presumably they interact through looping with nearby genes to modulate transcription. Hi-C provides the most complete and unbiased method for genome-wide identification of potential regulatory interactions, but finding chromatin loops in Hi-C data remains difficult and tissue specific data are limited. We have generated Hi-C data from primary cardiac tissue and developed a method, peakHiC, for sensitive and quantitative loop calling to uncover the human heart regulatory interactome. We identify complex CTCF-dependent and -independent contact networks, with loops between coding and non-coding gene promoters, shared enhancers and repressive sites. Across the genome, enhancer interaction strength correlates with gene transcriptional output and loop dynamics follows CTCF, cohesin and H3K27Ac occupancy levels. Finally, we demonstrate that intersection of the human heart regulatory interactome with cardiovascular disease variants facilitates prioritizing disease-causative genes.

Authors

Bianchi V  •  Geeven G  •  Tucker N  •  Hilvering CRE  •  Hall AW  •  Roselli C  •  Hill MC  •  Martin JF  •  Margulies KB  •  Ellinor PT  •  deLaat W

Link

http://biorxiv.org/lookup/doi/10.1101/705715


Journal

bioRxiv

doi:10.1101/705715

Published

July 17th, 2019