Epigenome regulation for coupling of SAM synthesis and histone methylation

SAM 合成和组蛋白甲基化耦合的表观基因组调控

• 批准号: 23790321
• 负责人: KATOH Yasutake
• 金额: $ 2.75万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790321/
• 关键词: ゲノム医化学; エピゲノム制御; 転写制御; S-アデノシルメチオニン; メチオニンアデノシル転移酵素; 細胞内局在; プロテオミクス解析; メチル基転移酵素

Histone and DNA methyltransferases utilized S-adenosyl-L-methioine (SAM, or AdoMet), a key intermediate of sulfur amino acid metabolism, as a donor of methyl group. SAM is biosynthesized by methionine adenosyltransferase (MAT) using two substrates, methionine and ATP. Three distinct forms of MAT (MATI, MATII and MATIII), encoded by two distinct genes (MAT1A and MAT2A), have been identified in mammals. MATII consists of α2 catalytic subunit encoded by MAT2A and β regulatory subunit encoded by MAT2B, but the physiological function of the β subunit is till unknown. MATII serves as a transcriptional corepressor in the oxidative stress response and forms the SAM-integrating transcription regulation module (SAMIT), affecting histone methyltransferase activities. However, the identities of genes regulated by MATIIα and β or its associated methyltransferases are unclear. My collaborators and I show that MATII 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.

组蛋白和DNA甲基转移酶利用硫氨基酸代谢的关键中间体s -腺苷- l-蛋氨酸（SAM，或AdoMet）作为甲基的供体。SAM是由蛋氨酸腺苷转移酶（methionine adenosyltransferase， MAT）利用蛋氨酸和ATP两种底物合成的。在哺乳动物中已经鉴定出三种不同形式的MAT (MATI， MATII和MATIII)，由两个不同的基因（MAT1A和MAT2A）编码。MATII由MAT2A编码的α2催化亚基和MAT2B编码的β调控亚基组成，但β亚基的生理功能尚不清楚。MATII在氧化应激反应中作为转录辅抑制因子，形成sam整合转录调节模块（SAMIT），影响组蛋白甲基转移酶活性。然而，受MATIIα和β或其相关甲基转移酶调控的基因的身份尚不清楚。我和我的合作者表明，MATII通过特异性地与组蛋白H3K9甲基转移酶SETDB1相互作用，抑制Ptgs2编码的环氧合酶2 （COX-2）的表达，从而促进H3K9在COX-2位点的三甲基化。我们讨论了MATII的基因特异性和表观基因组功能。

项目成果

メチオニンアデノシル転移酵素(MATII)の細胞内局在とその制御機構」「転写代謝システム

“蛋氨酸腺苷转移酶（MATII）的细胞内定位及其调控机制”“转录代谢系统”

• 发表时间: 2012
• 作者: 加藤恭丈;石山駿;森野杏子;槙野絵里子;五十嵐和彦
• 通讯作者: 五十嵐和彦

SAMIT module for coupling of S-adenosyl-L-methionine synthesis and chromatin regulation

SAMIT 模块用于耦合 S-腺苷-L-甲硫氨酸合成和染色质调控

• 发表时间: 2011
• 作者: Katoh Y;Morino K;Kera Y;Ohta M,Igarashi K.
• 通讯作者: Ohta M,Igarashi K.