title: RING1A and BMI1 bookmark active genes via ubiquitination of chromatin-associated proteins.
abstract: During mitosis the chromatin undergoes dramatic architectural changes with the halting of the transcriptional processes and evacuation of nearly all transcription associated machinery from genes and promoters. Molecular bookmarking of genes during mitosis is a mechanism of faithfully transmitting cell-specific transcription patterns through cell division. We previously discovered chromatin ubiquitination at active promoters as a potential mitotic bookmark. In this study, we identify the enzymes involved in the deposition of ubiquitin before mitosis. We find that the polycomb complex proteins BMI1 and RING1A regulate the ubiquitination of chromatin associated proteins bound to promoters, and this modification is necessary for the expression of marked genes once the cells enter G1. Depletion of RING1A, and thus inactivation of mitotic bookmarking by ubiquitination, is deleterious to progression through G1, cell survival and proliferation. Though the polycomb complex proteins are thought to primarily regulate gene expression by transcriptional repression, in this study, we discover that these two polycomb proteins regulate the transcription of active genes during the mitosis to G1 transition.
authors.affiliation: Department of Biomedical Informatics, OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Mansi
authors.initials: M
authors.lastname: Arora
authors.affiliation: Department of Biomedical Informatics, OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Colin Z
authors.initials: CZ
authors.lastname: Packard
authors.affiliation: Department of Biomedical Informatics, OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Tapahsama
authors.initials: T
authors.lastname: Banerjee
authors.affiliation: Department of Biomedical Informatics, OSU Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA Jeffrey.Parvin@osumc.edu.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Parvin
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D016193:G1 Phase / Q000235:genetics*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D063150:Polycomb Repressive Complex 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D054875:Ubiquitination
chemical_list: C069077:BMI1 protein, human; D002843:Chromatin; D006657:Histones; D034741:RNA, Small Interfering; D063150:Polycomb Repressive Complex 1; C080355:RING1 protein, human