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

作者：Hsiung Chris C S; Bartman Caroline R; Huang Peng; Ginart Paul; Stonestrom Aaron J; Keller Cheryl A; Face Carolyne; Jahn Kristen S; Evans Perry; Sankaranarayanan Laavanya; Giardine Belinda; Hardison Ross C; Raj Arjun; Blobel Gerd A^*

来源：Genes & Development, 2016, 30(12): 1423-1439.

DOI：10.1101/gad.280859.116

• chromatin
• epigenetics
• mitosis
• transcription

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, similar to 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.

• 出版日期2016-6-15