GSE138928
The transcriptional and architectural resetting of stem cell identity during G1 entry [PRO-Seq]
The molecular identity of dividing cells is temporarily challenged during mitosis, as transcription is halted and chromatin architecture is drastically altered. The principles and key players that ensure faithful propagation of cell identity upon G1 entry in the daughter cells remain elusive. Here, we used rapidly dividing mouse pluripotent stem cell (PSC) as a study model to characterize for the first time the dynamic transcriptional and architectural resetting of cell identity during mitotic exit, and assess the role of mitotic bookmarking by the active histone mark H3K27 acetylation (H3K27ac). Globally, compartments and topologically associating domains (TADs) were quickly reformed and gradually gained strength and activity throughout G1, while long-range chromatin interactions were reestablished at a slower rate. Binding of PSC-specific transcription factors (TFs) and transcriptional machinery associated with faster boundary insulation and contact formation, while CTCF, Cohesin and Polycomb-bound regions were characterized by a slower architectural resetting. Similarly, transcriptional reactivation of both PSC enhancers and their target genes occurred in early G1, while enhancers and genes involved in housekeeping/cell cycle or differentiation processes were activated in a gradual or transient manner, respectively. Mitotic bookmarking by H3K27ac promoted faster compartmentalization, boundary insulation, and loop formation, as well as rapid transcriptional reactivation. Interestingly, we identified a group of developmental genes and enhancers that were transiently activated in G1 and were marked by H3K27ac specifically during mitosis. This study provides insights into the relative kinetics of transcriptional and architectural rewiring after mitosis and establishes a unique role for H3K27ac bookmarking in the resetting of stem cell identity. Overall design: Ttranscriptional and architectural changes of iPSCs after mitotic exit