title: The aurora B kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes.
abstract: Reversible cellular quiescence is critical for developmental processes in metazoan organisms and is characterized by a reduction in cell size and transcriptional activity. We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes. Ring1B and Aurora B bind to a wide range of active promoters in resting B and T cells. Conditional knockout of either protein results in reduced transcription and binding of RNA Pol II to promoter regions and decreased cell viability. Aurora B phosphorylates histone H3S28 at active promoters in resting B cells as well as inhibiting Ring1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes. Our results identify a mechanism for regulating transcription in quiescent cells that has implications for epigenetic regulation of the choice between proliferation and quiescence.
authors.affiliation: Gene Regulation and Chromatin Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Campus, London W12 0NN, UK.
authors.forename: Alberto
authors.initials: A
authors.lastname: Frangini
authors.forename: Marcela
authors.initials: M
authors.lastname: Sjöberg
authors.forename: Monica
authors.initials: M
authors.lastname: Roman-Trufero
authors.forename: Gopuraja
authors.initials: G
authors.lastname: Dharmalingam
authors.forename: Vanja
authors.initials: V
authors.lastname: Haberle
authors.forename: Till
authors.initials: T
authors.lastname: Bartke
authors.forename: Boris
authors.initials: B
authors.lastname: Lenhard
authors.forename: Marcos
authors.initials: M
authors.lastname: Malumbres
authors.forename: Miguel
authors.initials: M
authors.lastname: Vidal
authors.forename: Niall
authors.initials: N
authors.lastname: Dillon
mesh_terms: D000818:Animals; D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006657:Histones / Q000378:metabolism; D051379:Mice; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D006657:Histones; C584021:Usp16 protein, mouse; C585419:UBE2D3 protein, mouse; D044763:Ubiquitin-Conjugating Enzymes; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D012319:RNA Polymerase II; D043222:Ubiquitin Thiolesterase