R-loops shape chromatin architecture to promote balanced lineage allocation during differentiation.

ABSTRACT: R-loops-RNA:DNA hybrids that often form co-transcriptionally-are emerging as key regulators of genome function, yet their roles in shaping chromatin architecture and developmental potential remain incompletely defined. Here, we use inducible Rnaseh1 expression in mouse embryonic stem cells (mESCs) to achieve acute, global R-loop depletion and systematically interrogate their impact on chromatin structure and lineage specification. We find that R-loop loss has minimal effect on steady-state gene expression or self-renewal. Instead, it leads to a striking reduction in H2A.Z occupancy at both active and bivalent promoters, accompanied by increased nucleosome density-revealing a previously unrecognized role for R-loops in maintaining promoter architecture. During gastruloid differentiat

SUBMITTER: Chao CH 

PROVIDER: S-EPMC12262388 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature