Coupring mechanism of methionine metabolism and epigenome

2015 Fiscal Year Final Research Report

• Project Area: Crosstalk of transcriptional control and energy pathways by hub metabolites
• Project/Area Number: 23116003
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tohoku University
• Principal Investigator: IGARASHI Kazuhiko 東北大学, 医学(系)研究科(研究院), 教授 (00250738)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: 発現制御 / 発生・分化 / プロテオーム / マイクロアレイ / 免疫学

Outline of Final Research Achievements

Regulation of epigenome relies on methylation of DNA and histones, which utilizes S-adenosyl-L-methoinine (SAM) as a sole methyl donor. SAM is synthesized by methionine adenosyltransferase (MAT) using methionine and ATP as substrates. In this research project, we discovered the molecular mechanism for the nuclear accumulation of MATII, one of the isozyme of MAT in higher eukaryotes. We also found that nuclear MATII interacted with various chromatin and transcription regulators, promoted histone H3 lysine 9 trimethylation of its target genes, and thus repress their expression. MATII also promoted formation of heterochromatin structure of certain chromatin subregions. These observations support our original contention that SAM is synthesized in nuclei for chromatin and gene expression (“local synthesis of SAM for local consumption” model). Next important step will be to understand how the activity of nuclear SAM is regulated during cell differentiation and/or proliferation.

Free Research Field

医歯薬学