Topologically associating domain boundaries that are stable across diverse cell types are evolutionarily constrained and enriched for heritability.

ABSTRACT: Topologically associating domains (TADs) are fundamental units of three-dimensional (3D) nuclear organization. The regions bordering TADs-TAD boundaries-contribute to the regulation of gene expression by restricting interactions of cis-regulatory sequences to their target genes. TAD and TAD-boundary disruption have been implicated in rare-disease pathogenesis; however, we have a limited framework for integrating TADs and their variation across cell types into the interpretation of common-trait-associated variants. Here, we investigate an attribute of 3D genome architecture-the stability of TAD boundaries across cell types-and demonstrate its relevance to understanding how genetic variation in TADs contributes to complex disease. By synthesizing TAD maps across 37 diverse cell types with 41

SUBMITTER: McArthur E 

PROVIDER: S-EPMC7895846 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature