Selective Recognition of H3.1K36 Dimethylation/H4K16 Acetylation Facilitates the Regulation of All-trans-retinoic Acid (ATRA)-responsive Genes by Putative Chromatin Reader ZMYND8
Selective Recognition of H3.1K36 Dimethylation/H4K16 Acetylation Facilitates the Regulation of All-trans-retinoic Acid (ATRA)-responsive Genes by Putative Chromatin Reader ZMYND8
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DOI：
10.1074/jbc.m115.679985
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发表时间：
2016-02-05
影响因子：
4.8
通讯作者：
Das, Chandrima
中科院分区：
文献类型：
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作者：
Adhikary, Santanu;Sanyal, Sulagna;Das, Chandrima
ZMYND8(ZMYND8)是一个新发现的转录辅助调节网络的组成部分，它与核小体重塑和去乙酰化酶(NuRD)复合体相互作用。以往的报道表明，ZMYND8有助于将NuRD复合体募集到受损的染色质上，以抑制转录，并通过同源重组促进双链断裂修复。然而，ZMYND8的转录调控模式仍然不清楚。在这里，我们报道了ZMYND8通过其保守的染色质结合模块中存在的特定关键残基与选择性表观遗传标记H3.1K36Me2/H4K16Ac相互作用。此外，ZMYND8显示出明显的对典型组蛋白H3.1的偏好，而不是变异体H3.3。有趣的是，ZMYND8被发现通过其修饰的组蛋白结合能力被招募到几个发育基因上，包括全反式维甲酸(ATRA)反应基因。这种锌指转录因子本身可被全反式维甲酸诱导，参与调节其他全反式维甲酸诱导基因。我们发现ZMYND8以DNA模板依赖的方式与Ser-5处磷酸化的转录起始RNA聚合酶II相互作用，并能改变整体基因的转录。总体而言，我们的研究发现，ZMYND8通过其修饰的组蛋白结合能力，在调控基因表达方面具有CHD4不依赖的功能。
ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8), a newly identified component of the transcriptional coregulator network, was found to interact with the Nucleosome Remodeling and Deacetylase (NuRD) complex. Previous reports have shown that ZMYND8 is instrumental in recruiting the NuRD complex to damaged chromatin for repressing transcription and promoting double strand break repair by homologous recombination. However, the mode of transcription regulation by ZMYND8 has remained elusive. Here, we report that through its specific key residues present in its conserved chromatin-binding modules, ZMYND8 interacts with the selective epigenetic marks H3.1K36Me2/H4K16Ac. Furthermore, ZMYND8 shows a clear preference for canonical histone H3.1 over variant H3.3. Interestingly, ZMYND8 was found to be recruited to several developmental genes, including the all-trans-retinoic acid (ATRA)responsive ones, through its modified histone-binding ability. Being itself inducible by ATRA, this zinc finger transcription factor is involved in modulating other ATRA-inducible genes. We found that ZMYND8 interacts with transcription initiation-competent RNA polymerase II phosphorylated at Ser-5 in a DNA template-dependent manner and can alter the global gene transcription. Overall, our study identifies that ZMYND8 has CHD4-independent functions in regulating gene expression through its modified histone-binding ability.