组蛋白甲基转移酶

组蛋白甲基转移酶（，简称为HMT）是包括组蛋白-赖氨酸N-甲基转移酶与组蛋白-精氨酸N-甲基转移酶在内的是一大類组蛋白修饰酶类，它们催化将一个、两个或三个甲基转移到组蛋白的赖氨酸或精氨酸残基上。被添加上的甲基基团主要位于组蛋白H3和H4的特定赖氨酸或精氨酸上。

种类
赖氨酸特异性组蛋白甲基转移酶类可被细分为含SET结构域的和不含SET结构域的两类。顾名思义，它们之间的区别在于存不存在SET这样一种结构域。

人类基因所编码的具有组蛋白甲基转移酶活性的蛋白质包括：

• ASH1L
• DOT1L
• EHMT1、EHMT2、EZH1、EZH2
• MLL、MLL2、MLL3、MLL4、MLL5
• NSD1
• PRDM2
• SET、SETBP1、SETD1A、SETD1B、SETD2、SETD3、SETD4、SETD5、SETD6、SETD7、SETD8、SETD9、SETDB1、SETDB2
• SETMAR、SMYD1、SMYD2、SMYD3、SMYD4、SMYD5、SUV39H1、SUV39H2、SUV420H1、SUV420H2

含SET结构域的赖氨酸特异性组蛋白甲基转移酶
结构
影响甲基转移酶活性的结构包括：SET结构域（包括130个氨基酸）、前SET和后SET结构域。前SET区域包括半胱氨酸残基，可形成三角锌簇，紧密结合锌原子并使结构稳定。SET结构域本身包含一个富含β-股的催化核心，从而形成几个β折叠区域。 一般在前SET结构域发现的β-股将形成的β-折叠，它带有SET结构域的β-股，导致SET结构域结构的细微变化。

These small changes alter the target residue site specificity for methylation and allow the SET domain methyltransferases to target many different residues. This interplay between the pre-SET domain and the catalytic core is critical for enzyme function.The lysine chain then makes a nucleophilic attack on the methyl group on the sulfur atom of the SAM molecule, transferring the methyl group to the lysine side chain.

不含SET结构域的赖氨酸特异性组蛋白甲基转移酶
Instead of SET, non-SET domain-containing histone methyltransferase utilizes the enzyme Dot1. Unlike the SET domain, which targets the lysine tail region of the histone, Dot1 methylates a lysine residue in the globular core of the histone, and is the only enzyme known to do so.Due to structural constraints, Dot1 is only able to methylate histone H3.

精氨酸特异性组蛋白甲基转移酶
There are two different types of protein arginine methyltransferases (PRMTs) and three types of methylation that can occur at arginine residues on histone tails. The first type of PRMTs (PRMT1, PRMT3, CARM1⧸PRMT4, and Rmt1⧸Hmt1) produce monomethylarginine and asymmetric dimethylarginine.The second type (JBP1⧸PRMT5) produces monomethyl or symmetric dimethylarginine.which can then make a nucleophilic attack on the methyl group of SAM. Differences between the two types of PRMTs determine the next methylation step: either catalyzing the dimethylation of one nitrogen or allowing the symmetric methylation of both groups.

在基因调控中的作用
Histone methylation plays an important role in epigenetic gene regulation. Methylated histones can either repress or activate transcription as different experimental findings suggest. For example, it is likely that the methylation of lysine 9 on histone H3 (H3K9me3) in the promoter region of genes prevents excessive expression of these genes and, therefore, delays cell cycle transition and/or proliferation.In recent years, epigenetic modification of the histone proteins, especially the methylation of the histone H3, in cancer development has been an area of emerging research. It is now generally accepted that in addition to genetic aberrations, cancer can be initiated by epigenetic changes in which gene expression is altered without genomic abnormalities. These epigenetic changes include loss or gain of methylations in both DNA and histone proteins.

进一步研究
组蛋白甲基转移酶可以用作癌症的诊断和预后的生物标志物。 另外，关于组蛋白甲基转移酶在细胞的恶性转化，组织的癌发生和肿瘤发生中的功能和调节仍然存在许多问题。

另见
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*组蛋白乙酰转移酶（HAT）
*组蛋白脱乙酰酶（HDAC）
*组蛋白甲基化
*核小體
*染色质

参考文献
深入阅读
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外部链接

• [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=kleefstra GeneReviews/NCBI/NIH/UW entry on Kleefstra Syndrome]

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