Transcription Restart Establishes Chromatin Accessibility after DNA Replication.

Autor:	Stewart-Morgan KR; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; The Novo Nordisk Center for Protein Research (CPR), University of Copenhagen, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Reverón-Gómez N; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; The Novo Nordisk Center for Protein Research (CPR), University of Copenhagen, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark., Groth A; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; The Novo Nordisk Center for Protein Research (CPR), University of Copenhagen, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: anja.groth@bric.ku.dk.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2019 Jul 25; Vol. 75 (2), pp. 284-297.e6. Date of Electronic Publication: 2019 May 21.
DOI:	10.1016/j.molcel.2019.04.033
Abstrakt:	DNA replication is highly disruptive to chromatin, leading to eviction of nucleosomes, RNA polymerase, and regulatory factors. When and how transcription resumes on DNA following DNA replication is unknown. Here we develop a replication-coupled assay for transposase-accessible chromatin (repli-ATAC-seq) to investigate active chromatin restoration post-replication in mouse embryonic stem cells. We find that nascent chromatin is inaccessible and transcriptionally silenced, with accessibility and RNA polymerase occupancy re-appearing within 30 minutes. Chromatin accessibility restores differentially genome wide, with super enhancers regaining transcription factor occupancy faster than other genomic features. We also identify opportunistic and transiently accessible chromatin within gene bodies after replication. Systematic inhibition of transcription shows that transcription restart is required to re-establish active chromatin states genome wide and resolve opportunistic binding events resulting from DNA replication. Collectively, this establishes a central role for transcription in overcoming the genome-wide chromatin inaccessibility imposed by DNA replication every cell division. (Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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