Kim Hyun-Soo, Mukhopadhyay Rituparna, Rothbart Scott B, Silva Andrea C, Vanoosthuyse Vincent, Radovani Ernest, Kislinger Thomas, Roguev Assen, Ryan Colm J, Xu Jiewei, Jahari Harlizawati, Hardwick Kevin G, Greenblatt Jack F, Krogan Nevan J, Fillingham Jeffrey S, Strahl Brian D, Bouhassira Eric E, Edelmann Winfried, Keogh Michael-Christopher
Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10454, USA.
Department of Biochemistry and Biophysics, UNC School of Medicine, Chapel Hill, NC 27599, USA.
Cell Rep. 2014 Mar 13;6(5):892-905. doi: 10.1016/j.celrep.2014.01.029. Epub 2014 Feb 22.
Condensin is a central regulator of mitotic genome structure with mutants showing poorly condensed chromosomes and profound segregation defects. Here, we identify NCT, a complex comprising the Nrc1 BET-family tandem bromodomain protein (SPAC631.02), casein kinase II (CKII), and several TAFs, as a regulator of condensin function. We show that NCT and condensin bind similar genomic regions but only briefly colocalize during the periods of chromosome condensation and decondensation. This pattern of NCT binding at the core centromere, the region of maximal condensin enrichment, tracks the abundance of acetylated histone H4, as regulated by the Hat1-Mis16 acetyltransferase complex and recognized by the first Nrc1 bromodomain. Strikingly, mutants in NCT or Hat1-Mis16 restore the formation of segregation-competent chromosomes in cells containing defective condensin. These results are consistent with a model where NCT targets CKII to chromatin in a cell-cycle-directed manner in order to modulate the activity of condensin during chromosome condensation and decondensation.
凝缩素是有丝分裂基因组结构的核心调节因子,其突变体表现出染色体凝聚不良和严重的分离缺陷。在这里,我们鉴定出NCT,这是一种由Nrc1 BET家族串联溴结构域蛋白(SPAC631.02)、酪蛋白激酶II(CKII)和几种TAF组成的复合物,作为凝缩素功能的调节因子。我们发现NCT和凝缩素结合相似的基因组区域,但仅在染色体凝聚和去凝聚期间短暂共定位。NCT在核心着丝粒(凝缩素富集程度最高的区域)的这种结合模式,追踪了由Hat1-Mis16乙酰转移酶复合物调节并被第一个Nrc1溴结构域识别的乙酰化组蛋白H4的丰度。引人注目的是,NCT或Hat1-Mis16中的突变体可恢复含有缺陷凝缩素的细胞中具有分离能力的染色体的形成。这些结果与一个模型一致,即NCT以细胞周期定向的方式将CKII靶向染色质,以便在染色体凝聚和去凝聚过程中调节凝缩素的活性。