The Aurora B Kinase and the Polycomb Protein Ring1B Combine to Regulate Active Promoters in Quiescent Lymphocytes

被引:91
作者
Frangini, Alberto [1 ]
Sjoeberg, Marcela [1 ]
Roman-Trufero, Monica [1 ]
Dharmalingam, Gopuraja [1 ]
Haberle, Vanja [2 ]
Bartke, Till [3 ]
Lenhard, Boris [2 ]
Malumbres, Marcos [4 ,5 ]
Vidal, Miguel [6 ]
Dillon, Niall [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Gene Regulat & Chromatin Grp, London W12 0NN, England
[2] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Computat Regulatory Genom Grp, London W12 0NN, England
[3] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Chromatin Biochem Grp, London W12 0NN, England
[4] Spanish Natl Canc Res Ctr CNIO, Cell Div, E-28029 Madrid, Spain
[5] Spanish Natl Canc Res Ctr CNIO, Canc Grp, E-28029 Madrid, Spain
[6] CSIC, Ctr Invest Biol, Madrid 28040, Spain
基金
英国医学研究理事会;
关键词
CELL-CYCLE PROGRESSION; RNA-POLYMERASE-II; HISTONE H3; GENE-EXPRESSION; PHOSPHORYLATION; COMPLEX; H2A; ACTIVATION; CHROMATIN; UBIQUITINATION;
D O I
10.1016/j.molcel.2013.08.022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:647 / 661
页数:15
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