<i>Trans</i>-regulation of heterochromatin underlies genetic variation in 3D genome contacts.

ABSTRACT: Genetic variation drives phenotypic diversity and disease susceptibility. Trans-acting genetic variation coordinates genome-wide chromatin changes, yet the molecular mechanisms underlying this regulation remain unclear. Here, we use the power of mouse genetics to investigate how genetic variation at trans-acting loci regulates 3D chromatin interactions. Using HiChIP to map H3K27ac-associated regulatory elements in C57BL/6J and DBA/2J embryonic stem cells (ESCs), we identified 4,962 strain-differential interactions, 71% of which overlapped chromatin accessibility quantitative trait loci (QTL), establishing chromatin interaction variation is predominantly heritable. These differential interactions showed coordinated changes in chromatin state and gene expression, with stronger

SUBMITTER: Fortin HJ 

PROVIDER: S-EPMC12712905 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature