RT Journal Article
SR Electronic
T1 A hyperactive transcriptional state marks genome reactivation at the mitosis-G1 transition
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 053678
DO 10.1101/053678
A1 Chris C.-S. Hsiung
A1 Caroline Bartman
A1 Peng Huang
A1 Paul Ginart
A1 Aaron J. Stonestrom
A1 Cheryl A. Keller
A1 Carolyne Face
A1 Kristen S. Jahn
A1 Perry Evans
A1 Laavanya Sankaranarayanan
A1 Belinda Giardine
A1 Ross C. Hardison
A1 Arjun Raj
A1 Gerd A. Blobel
YR 2016
UL http://biorxiv.org/content/early/2016/05/17/053678.abstract
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.