title: Promoters active in interphase are bookmarked during mitosis by ubiquitination.
abstract: We analyzed modification of chromatin by ubiquitination in human cells and whether this mark changes through the cell cycle. HeLa cells were synchronized at different stages and regions of the genome with ubiquitinated chromatin were identified by affinity purification coupled with next-generation sequencing. During interphase, ubiquitin marked the chromatin on the transcribed regions of ∼70% of highly active genes and deposition of this mark was sensitive to transcriptional inhibition. Promoters of nearly half of the active genes were highly ubiquitinated specifically during mitosis. The ubiquitination at the coding regions in interphase but not at promoters during mitosis was enriched for ubH2B and dependent on the presence of RNF20. Ubiquitin labeling of both promoters during mitosis and transcribed regions during interphase, correlated with active histone marks H3K4me3 and H3K36me3 but not a repressive histone modification, H3K27me3. The high level of ubiquitination at the promoter chromatin during mitosis was transient and was removed within 2 h after the cells exited mitosis and entered the next cell cycle. These results reveal that the ubiquitination of promoter chromatin during mitosis is a bookmark identifying active genes during chromosomal condensation in mitosis, and we suggest that this process facilitates transcriptional reactivation post-mitosis.
authors.affiliation: Department of Biomedical Informatics and the Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Mansi
authors.initials: M
authors.lastname: Arora
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: George F
authors.initials: GF
authors.lastname: Heine
authors.forename: Gulcin
authors.initials: G
authors.lastname: Ozer
authors.forename: Hui-wen
authors.initials: HW
authors.lastname: Liu
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Parvin
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D002843:Chromatin / Q000378:metabolism*; D016678:Genome; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D007399:Interphase / Q000235:genetics*; D008938:Mitosis / Q000235:genetics*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic / Q000187:drug effects; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases / Q000502:physiology; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D002843:Chromatin; D006657:Histones; D019384:Nucleic Acid Synthesis Inhibitors; D025801:Ubiquitin; C506646:RNF20 protein, human; D044767:Ubiquitin-Protein Ligases