| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
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.
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