ZNF198 stabilizes the LSD1-CoREST-HDAC1 complex on chromatin through its MYM-type zinc fingers.
ZNF198 stabilizes the LSD1-CoREST-HDAC1 complex on chromatin through its MYM-type zinc fingers.
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DOI：
10.1371/journal.pone.0003255
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发表时间：
2008-09-22
期刊：
影响因子：
3.7
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Gocke CB;Yu H
染色质中的组蛋白修饰调节基因表达。含有LSD 1-CoREST-HDAC 1（为简单起见，下文称为LCH）的转录共阻遏物复合物通过协同去除与转录激活相关的组蛋白修饰来阻遏转录。RE 1沉默转录因子（REST）将LCH募集到神经元特异性基因的启动子，从而沉默它们在非神经元组织中的转录。ZNF 198是与LCH相关的MYM型锌指蛋白家族的成员。在这里，我们表明，ZNF 198样蛋白的抑制所需的E-钙粘蛋白（一个基因被LSD 1抑制），但不是REST响应基因。ZNF 198优先结合完整的LCH三元复合物，但不是其单个亚基。ZNF 198和REST与LCH复合物的结合是相互排斥的。ZNF 198与染色质的结合不依赖于LCH。此外，HDAC 1的小泛素样修饰剂（SUMO）在体外的修饰减弱了其与CoREST的相互作用，而HDAC 1的SUMO化刺激其与ZNF 198的结合。最后，我们将ZNF 198的LCH-和HDAC 1-SUMO结合结构域定位到MYM型锌指的串联重复序列。因此，我们的结果表明，ZNF 198通过其多种蛋白质-蛋白质相互作用界面，有助于维持特定的非REST响应启动子上完整的LCH复合物，并且还可能阻止HDAC 1的SUMO依赖性解离。
Histone modifications in chromatin regulate gene expression. A transcriptional co-repressor complex containing LSD1–CoREST–HDAC1 (termed LCH hereafter for simplicity) represses transcription by coordinately removing histone modifications associated with transcriptional activation. RE1-silencing transcription factor (REST) recruits LCH to the promoters of neuron-specific genes, thereby silencing their transcription in non-neuronal tissues. ZNF198 is a member of a family of MYM-type zinc finger proteins that associate with LCH. Here, we show that ZNF198-like proteins are required for the repression of E-cadherin (a gene known to be repressed by LSD1), but not REST-responsive genes. ZNF198 binds preferentially to the intact LCH ternary complex, but not its individual subunits. ZNF198- and REST-binding to the LCH complex are mutually exclusive. ZNF198 associates with chromatin independently of LCH. Furthermore, modification of HDAC1 by small ubiquitin-like modifier (SUMO) in vitro weakens its interaction with CoREST whereas sumoylation of HDAC1 stimulates its binding to ZNF198. Finally, we mapped the LCH- and HDAC1–SUMO-binding domains of ZNF198 to tandem repeats of MYM-type zinc fingers. Therefore, our results suggest that ZNF198, through its multiple protein-protein interaction interfaces, helps to maintain the intact LCH complex on specific, non-REST-responsive promoters and may also prevent SUMO-dependent dissociation of HDAC1.
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影响因子：
64.5
作者：
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