Methionine Adenosyltransferase II-dependent Histone H3K9 Methylation at the COX-2 Gene Locus
Methionine Adenosyltransferase II-dependent Histone H3K9 Methylation at the COX-2 Gene Locus
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DOI：
10.1074/jbc.m112.429738
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发表时间：
2013-05-10
影响因子：
4.8
通讯作者：
Igarashi, Kazuhiko
中科院分区：
文献类型：
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作者：
Kera, Yohei;Katoh, Yasutake;Igarashi, Kazuhiko
蛋氨酸腺苷转移酶(MAT)合成S-腺苷蛋氨酸(ADOMet)，在涉及组蛋白的转甲基化反应中用作甲基供体。MATIIα是一种MAT同工酶，在氧化应激反应中作为转录辅阻遏子，形成ADOMet整合转录调控模块，影响组蛋白甲基转移酶的活性。然而，由MATIIα或与其相关的甲基转移酶调控的基因的身份尚不清楚。我们发现MATIIα通过与组蛋白H3K9甲基转移酶SETDB1特异性地相互作用来抑制由Ptgs2编码的环氧合酶2(COX-2)的表达，从而促进COX-2基因上H3K9的三甲基化。我们讨论了MATIIα的基因特异性和表观基因组范围的功能。
Methionine adenosyltransferase (MAT) synthesizes S-adenosylmethionine (AdoMet), which is utilized as a methyl donor in transmethylation reactions involving histones. MATII alpha, a MAT isozyme, serves as a transcriptional corepressor in the oxidative stress response and forms the AdoMet-integrating transcription regulation module, affecting histone methyltransferase activities. However, the identities of genes regulated by MATII alpha or its associated methyltransferases are unclear. We show that MATII alpha represses the expression of cyclooxygenase 2 (COX-2), encoded by Ptgs2, by specifically interacting with histone H3K9 methyltransferase SETDB1, thereby promoting the trimethylation of H3K9 at the COX-2 locus. We discuss both gene-specific and epigenome-wide functions of MATII alpha.