Components of the DNA methylation system of chromatin control are RNA-binding proteins
Components of the DNA methylation system of chromatin control are RNA-binding proteins
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DOI：
10.1074/jbc.m409070200
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发表时间：
2004-11-19
影响因子：
4.8
通讯作者：
Nakielny, S
中科院分区：
文献类型：
--
作者：
Jeffery, L;Nakielny, S
常染色体基因表达完全由蛋白质反式作用因子控制的观点最近受到了鉴定调节染色质的RNA分子的挑战。在RNA分子参与DNA控制的大多数情况下，分子机制是未知的，这在很大程度上是因为RNA蛋白质复合物没有被表征。在这里，我们确定了一组新的RNA结合蛋白，是众所周知的，他们的功能在染色质调控。RNA相互作用蛋白是哺乳动物DNA甲基化系统的组成部分。基因组甲基化在转座子沉默、印记和X染色体剂量补偿的背景下控制染色质。DNA甲基转移酶（DNMT）催化CG中胞嘧啶的甲基化。甲基-CG被甲基-DNA结合结构域（MBD）蛋白识别，其募集组蛋白脱乙酰酶和染色质重塑蛋白以实现沉默。我们表明，DNMT和MBD蛋白的一个子集可以形成RNA蛋白复合物。我们的MBD蛋白的RNA结合活性的特点，并表明，它是不同的甲基CG结合结构域和介导的高亲和力与RNA的相互作用。MBD蛋白的RNA和甲基-CG结合特性是相互排斥的。我们推测DNMT和MBD蛋白允许RNA分子参与DNA甲基化介导的染色质控制。
The view that autosomal gene expression is controlled exclusively by protein trans-acting factors has been challenged recently by the identification of RNA molecules that regulate chromatin. In the majority of cases where RNA molecules are implicated in DNA control, the molecular mechanisms are unknown, in large part because the RNA.protein complexes are uncharacterized. Here, we identify a novel set of RNA-binding proteins that are well known for their function in chromatin regulation. The RNA-interacting proteins are components of the mammalian DNA methylation system. Genomic methylation controls chromatin in the context of transposon silencing, imprinting, and X chromosome dosage compensation. DNA methyltransferases (DNMTs) catalyze methylation of cytosines in CGs. The methyl-CGs are recognized by methyl-DNA-binding domain (MBD) proteins, which recruit histone deacetylases and chromatin remodeling proteins to effect silencing. We show that a subset of the DNMTs and MBD proteins can form RNA.protein complexes. We characterize the MBD protein RNA-binding activity and show that it is distinct from the methyl-CG-binding domain and mediates a high affinity interaction with RNA. The RNA and methyl-CG binding properties of the MBD proteins are mutually exclusive. We speculate that DNMTs and MBD proteins allow RNA molecules to participate in DNA methylation-mediated chromatin control.