title: A hyperactive transcriptional state marks genome reactivation at the mitosis-G1 transition.
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.
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Chris C-S
authors.initials: CC
authors.lastname: Hsiung
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Caroline R
authors.initials: CR
authors.lastname: Bartman
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA, Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Paul
authors.initials: P
authors.lastname: Ginart
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Stonestrom
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Keller
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Carolyne
authors.initials: C
authors.lastname: Face
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Kristen S
authors.initials: KS
authors.lastname: Jahn
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Perry
authors.initials: P
authors.lastname: Evans
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Laavanya
authors.initials: L
authors.lastname: Sankaranarayanan
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Belinda
authors.initials: B
authors.lastname: Giardine
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Ross C
authors.initials: RC
authors.lastname: Hardison
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Arjun
authors.initials: A
authors.lastname: Raj
authors.affiliation: Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Blobel
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D021901:DNA, Intergenic / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D004900:Erythroblasts / Q000166:cytology; D016193:G1 Phase / Q000235:genetics*; D016678:Genome / Q000235:genetics*; D051379:Mice; D008938:Mitosis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D002843:Chromatin; D021901:DNA, Intergenic
keywords: chromatin; epigenetics; mitosis; transcription