ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage
ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage
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DOI：
10.1016/j.celrep.2016.09.037
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发表时间：
2016-10-11
期刊：
影响因子：
8.8
通讯作者：
Vermeulen, Michiel
中科院分区：
文献类型：
--
作者：
Spruijt, Cornelia G.;Luijsterburg, Martijn S.;Vermeulen, Michiel
NuRD（核小体重塑和组蛋白去乙酰化酶）是一种多功能的多蛋白复合物，在转录调节和DNA损伤反应中发挥作用。在这里，我们发现ZMYND8将NuRD与许多假定的dna结合锌指蛋白连接起来。ZMYND8的MYND结构域直接与NuRD亚基GATAD2A中的PPPLF Phi基序相互作用。GATAD2A和GATAD2B都排他性地形成同型二聚体，并定义互斥的NuRD亚复合物。ZMYND8和NuRD具有大量的全基因组结合位点，主要是活性启动子和增强子。ZMYND8的缺失不影响NuRD的全基因组占用，仅轻微影响NuRD/ZMYND8靶基因的表达。相比之下，ZMYND8中的MYND结构域促进了GATAD2A/NuRD快速、多聚（adp -核糖）依赖性地募集到DNA损伤位点，从而促进同源重组修复。因此，这些结果表明，与NuRD亚基平行物的特定亚化学计量相互作用为不同的NuRD亚复合物提供了独特的功能。
NuRD (nucleosome remodeling and histone deacetylase) is a versatile multi-protein complex with roles in transcription regulation and the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The MYND domain of ZMYND8 directly interacts with PPPLF Phi motifs in the NuRD subunit GATAD2A. Both GATAD2A and GATAD2B exclusively form homodimers and define mutually exclusive NuRD subcomplexes. ZMYND8 and NuRD share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and only slightly affects expression of NuRD/ZMYND8 target genes. In contrast, the MYND domain in ZMYND8 facilitates the rapid, poly(ADP-ribose)-dependent recruitment of GATAD2A/NuRD to sites of DNA damage to promote repair by homologous recombination. Thus, these results show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to distinct NuRD subcomplexes.