Insulation between adjacent TADs is controlled by the width of their boundaries through distinct mechanisms.

ABSTRACT: Topologically associating domains (TADs) are sub-Megabase regions in vertebrate genomes with enriched intradomain interactions that restrict enhancer-promoter contacts across their boundaries. However, the mechanisms that separate TADs remain incompletely understood. Most boundaries between TADs contain CTCF binding sites (CBSs), which individually contribute to the blocking of Cohesin-mediated loop extrusion. Using genome-wide classification, here we show that the width of TAD boundaries forms a continuum from narrow to highly extended and correlates with CBSs distribution, chromatin features, and gene regulatory elements. To investigate how these boundary widths emerge, we modified the random crosslinker polymer model to incorporate specific boundary configurations, enabling us to evalua

SUBMITTER: Papale A 

PROVIDER: S-EPMC11929393 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature