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Genes Dev. 2016 Jun 15;30(12):1423-39. doi: 10.1101/gad.280859.116.

A hyperactive transcriptional state marks genome reactivation at the mitosis-G1 transition.

Author information

1
Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
2
Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
3
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA, Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
4
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.

Abstract

During mitosis, RNA polymerase II (Pol II) and many transcription factors dissociate from chromatin, and transcription ceases globally. Transcription is known to restart in bulk by telophase, but whether de novo transcription at the mitosis-G1 transition is in any way distinct from later in interphase remains unknown. We tracked Pol II occupancy genome-wide in mammalian cells progressing from mitosis through late G1. Unexpectedly, during the earliest rounds of transcription at the mitosis-G1 transition, ∼50% of active genes and distal enhancers exhibit a spike in transcription, exceeding levels observed later in G1 phase. Enhancer-promoter chromatin contacts are depleted during mitosis and restored rapidly upon G1 entry but do not spike. Of the chromatin-associated features examined, histone H3 Lys27 acetylation levels at individual loci in mitosis best predict the mitosis-G1 transcriptional spike. Single-molecule RNA imaging supports that the mitosis-G1 transcriptional spike can constitute the maximum transcriptional activity per DNA copy throughout the cell division cycle. The transcriptional spike occurs heterogeneously and propagates to cell-to-cell differences in mature mRNA expression. Our results raise the possibility that passage through the mitosis-G1 transition might predispose cells to diverge in gene expression states.

KEYWORDS:

chromatin; epigenetics; mitosis; transcription

PMID:
27340175
PMCID:
PMC4926865
DOI:
10.1101/gad.280859.116
[Indexed for MEDLINE]
Free PMC Article

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