Mitotic bookmarking by H3K27 acetylation is critical for rapid transcriptional, but not architectural, resetting of stem cell-related genes and enhancers upon G1 entry [PRO-seq]

ABSTRACT: The identity of dividing cells is challenged during mitosis, as transcription is halted and chromatin architecture drastically altered. How cell type-specific gene expression and genomic organization are faithfully reset upon G1 entry in daughter cells remains elusive. To address this issue, we characterized at a genome-wide scale the dynamic transcriptional and architectural resetting of mouse pluripotent stem cells (PSCs) upon mitotic exit. This revealed distinct patterns of transcriptional reactivation with rapid induction of stem cell genes and their enhancers, a more gradual recovery of metabolic and cell cycle genes, and a weak and transient activation of lineage-specific genes only during G1. Topological reorganization at different hierarchical levels also occurred in an asynchronous manner and showed an overall weak coordination with transcriptional reactivation. Chromatin interactions around active promoters and enhancers, and particularly super enhancers, reformed at a faster rate than CTCF/Cohesin-bound structural loops. Interestingly, although regions with mitotic retention of the active histone mark H3K27ac associated both with faster transcriptional and architectural resetting, depletion of this mark specifically during mitosis perturbed transcriptional reactivation of H3K27ac-bookmarked genes without affecting chromatin topology. Our study provides an integrative map of the topological and transcriptional changes that lead to the resetting of pluripotent stem cell identity during mitotic exit, and reveals distinct patterns and features that balance the dual requirements for self-renewal and differentiation.

ORGANISM(S): Mus musculus

PROVIDER: GSE164342 | GEO | 2021/03/01

REPOSITORIES: GEO