SHREC Silences Heterochromatin via Distinct Remodeling and Deacetylation Modules.
SHREC Silences Heterochromatin via Distinct Remodeling and Deacetylation Modules.
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DOI：
10.1016/j.molcel.2016.03.016
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发表时间：
2016-04-21
期刊：
影响因子：
16
通讯作者：
Schalch T
中科院分区：
文献类型：
--
作者：
Job G;Brugger C;Xu T;Lowe BR;Pfister Y;Qu C;Shanker S;Baños Sanz JI;Partridge JF;Schalch T
核小体重塑和去乙酰化（NuRD）复合物是与分化、发育和疾病有关的共转录调节因子。甲基-CpG结合结构域（MBD）蛋白在将NuRD复合物募集到其染色质中的靶位点中起重要作用。裂殖酵母中相关的SHREC复合体通过与HP 1蛋白的合作驱动异染色质中的转录基因沉默。重塑和组蛋白去乙酰化酶（HDAC）如何在NuRD复合物中合作仍然没有解决。我们确定，在SHREC中，这两个模块占据了支架蛋白Clr 1上的远端位点，并且SHREC的抑制活性可以单独通过HDAC相关Clr 1结构域的表达水平来调节。此外，Clr 2的晶体结构揭示了介导HDAC模块向异染色质募集的MBD样结构域。因此，SHREC双功能性被组织在两个独立的模块中，具有独立的募集机制，它们一起工作以引起异染色质基因座的转录沉默。
Nucleosome remodeling and deacetylation (NuRD) complexes are co-transcriptional regulators implicated in differentiation, development and diseases. Methyl-CpG Binding Domain (MBD) proteins play an essential role in recruitment of NuRD complexes to their target sites in chromatin. The related SHREC complex in fission yeast drives transcriptional gene silencing in heterochromatin through cooperation with HP1 proteins. How remodeler and histone deacetylase (HDAC) cooperate within NuRD complexes remains unresolved. We determined that in SHREC the two modules occupy distant sites on the scaffold protein Clr1, and that repressive activity of SHREC can be modulated by the expression level of the HDAC-associated Clr1 domain alone. Moreover, the crystal structure of Clr2 reveals an MBD-like domain mediating recruitment of the HDAC module to heterochromatin. Thus SHREC bi-functionality is organized in two separate modules with separate recruitment mechanisms, which work together to elicit transcriptional silencing at heterochromatic loci.