Gene Regulation and Chromatin Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Campus, London W12 0NN, UK.
Mol Cell. 2013 Sep 12;51(5):647-61. doi: 10.1016/j.molcel.2013.08.022.
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.
细胞可逆性静止对于多细胞生物的发育过程至关重要，其特征是细胞体积缩小和转录活性降低。我们表明，极光激酶 B 和多梳蛋白 Ring1B 在调节静止淋巴细胞中转录活性基因方面具有重要作用。Ring1B 和 Aurora B 结合到静止 B 和 T 细胞中广泛的活性启动子上。这两种蛋白质的条件敲除导致转录减少，RNA Pol II 与启动子区域结合减少，细胞活力降低。Aurora B 在静止 B 细胞的活跃启动子上磷酸化组蛋白 H3S28，同时抑制 Ring1B 介导的组蛋白 H2A 的泛素化，并增强 USP16 去泛素酶在转录基因上的结合和活性。我们的结果确定了一种调节静止细胞中转录的机制，这对增殖和静止之间的选择的表观遗传调控具有重要意义。
