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A new role for the transcriptional corepressor SIN3; Regulation of centromeres

机译:转录共受体SIN3的新作用;着丝粒的调节

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Centromeres play a vital role in maintaining the genomic stability of eukaryotes by coordinating the equal distribution of chromosomes to daughter cells during mitosis and meiosis. Fission yeast (S. pombe) centromeres consist of a 4-9 kb central core region and 30-100 kb of flanking inner (imr/B) and outer (otr/K) repeats [1-3]. These sequences direct a laminar kinetochore structure similar to that of human centromeres [4, 5]. Centromeric heterochromatin is generally underacetylated [6, 7]. We have previously shown that inhibition of histone deacetylases (HDACs) caused hyperacetylation of centromeres and defective chromosome segregation [8]. SIN3 is a HDAC corepressor that has the ability to mediate HDAC targeting in the repression of promoters. In this study, we have characterized S. pombe sin three corepressors (Pst1p and Pst2p) to investigate whether SIN3-HDAC is required in the regulation of centromeres. We show that only pst1-1 and not pst2Delta cells displayed anaphase defects and thiabendazole sensitivity. pst1-1 cells showed reduced centromeric silencing, increased histone acetylation in centromeric chromatin, and defective centromeric sister chromatid cohesion. The HDAC Clr6p and Pst1p coimmunoprecipitated, and Pst1p colocalized with centromeres, particularly in binucleate cells. These data are consistent with a model in which Pst1 pClr6p temporally associate with centromeres to carry out the initial deacetylation necessary for subsequent steps in heterochromatin formation.
机译:通过在有丝分裂和减数分裂过程中协调染色体在子细胞中的均匀分布,着丝粒在维持真核生物的基因组稳定性中起着至关重要的作用。裂变酵母(S. pombe)着丝粒由4-9 kb的中央核心区域和30-100 kb的侧翼内部重复序列(imr / B)和外部重复序列(otr / K)组成[1-3]。这些序列指导类似于人着丝粒[4,5]的层状线粒体结构。着丝粒的异染色质通常未充分乙酰化[6,7]。先前我们已经表明,抑制组蛋白脱乙酰基酶(HDACs)会引起着丝粒的过度乙酰化和有缺陷的染色体分离[8]。 SIN3是一种HDAC核心抑制剂,具有介导HDAC靶向抑制启动子的能力。在这项研究中,我们已经表征了粟酒裂殖酵母的三个核心加压因子(Pst1p和Pst2p),以研究在着丝粒调节中是否需要SIN3-HDAC。我们显示只有pst1-1,而不是pst2Delta细胞显示后期缺陷和噻苯达唑敏感性。 pst1-1细胞显示出降低的着丝粒沉默,着丝粒染色质中组蛋白乙酰化的增强和着丝粒姐妹染色单体内聚力的缺陷。 HDAC Clr6p和Pst1p共沉淀,Pst1p与着丝粒共定位,特别是在双核细胞中。这些数据与其中Pst1 pClr6p在时间上与着丝粒相关联以进行异染色质形成后续步骤所需的初始脱乙酰作用的模型一致。

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