PT  - JOURNAL ARTICLE
AU  - Chris C.-S. Hsiung
AU  - Caroline Bartman
AU  - Peng Huang
AU  - Paul Ginart
AU  - Aaron J. Stonestrom
AU  - Cheryl A. Keller
AU  - Carolyne Face
AU  - Kristen S. Jahn
AU  - Perry Evans
AU  - Laavanya Sankaranarayanan
AU  - Belinda Giardine
AU  - Ross C. Hardison
AU  - Arjun Raj
AU  - Gerd A. Blobel
TI  - A hyperactive transcriptional state marks genome reactivation at the mitosis-G1 transition
AID  - 10.1101/053678
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 053678
4099  - http://biorxiv.org/content/early/2016/05/17/053678.short
4100  - http://biorxiv.org/content/early/2016/05/17/053678.full
AB  - 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 lysine 27 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.