Dnmt3L is a transcriptional repressor that recruits histone deacetylase
Dnmt3L is a transcriptional repressor that recruits histone deacetylase
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DOI：
10.1093/nar/gkf509
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发表时间：
2002-09-01
影响因子：
14.9
通讯作者：
Fuks, F
中科院分区：
文献类型：
--
作者：
Deplus, R;Brenner, C;Fuks, F
Dnmt3L蛋白在植物同源结构域（PHD）样基序中具有序列同源性，属于DNA甲基转移酶Dnmt3家族。Dnmt3L对于母体基因组印记的建立至关重要，鉴于其缺乏关键的甲基转移酶基序，它更有可能作为甲基化的调节剂而不是甲基化DNA的酶。在这里，我们发现Dnmt3L，像Dnmt3a和Dnmt3b一样，在体外和体内都与组蛋白去乙酰化酶HDAC1相互作用。Dnmt3L与去乙酰化酶结合，从核提取物中纯化组蛋白去乙酰化酶活性。我们发现Dnmt3L可以抑制转录，这种抑制依赖于HDAC1，并通过HDAC抑制剂trichostatin a治疗而减轻。Dnmt3L与HDAC1的结合及其抑制功能需要博士样基序。我们的研究结果表明，Dnmt3L在转录调控中发挥作用，而HDAC抑制机制的募集是Dnmt3家族共有的和保守的特征。尽管缺乏甲基转移酶结构域，但Dnmt3L保留了与去乙酰化酶接触的能力，这一事实进一步证实了Dnmts可以独立于其甲基化活性抑制转录的观点。
The Dnmt3L protein belongs to the Dnmt3 family of DNA methyltransferases by virtue of its sequence homology in the plant homeodomain (PHD)-like motif. Dnmt3L is essential for the establishment of maternal genomic imprints and, given its lack of key methyltransferase motifs, is more likely to act as a regulator of methylation rather than as an enzyme that methylates DNA. Here, we show that Dnmt3L, like Dnmt3a and Dnmt3b, interacts both in vitro and in vivo with the histone deacetylase HDAC1. Consistent with the binding to a deacetylase, Dnmt3L purifies histone deacetylase activity from nuclear extracts. We find that Dnmt3L can repress transcription and that this repression is dependent on HDAC1 and is relieved by treatment with the HDAC inhibitor trichostatin A. Binding of Dnmt3L to HDAC1 as well as its repressive function require the PHD-like motif. Our results indicate that Dnmt3L plays a role in transcriptional regulation and that recruitment of the HDAC repressive machinery is a shared and conserved feature of the Dnmt3 family. The fact that, despite the absence of a methyltransferase domain, Dnmt3L retains the capacity to contact deacetylase further substantiates the notion that the Dnmts can repress transcription independently of their methylating activities.