Methods rewriting epigenome as the target of methyonine adenosyltransferase II

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460351
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: KATOH Yasutake 東北大学, 東北メディカル・メガバンク機構, 講師 (40397914)
• Co-Investigator(Renkei-kenkyūsha): MORITA Masanobu 東北大学, 医学系研究科, 助教 (10519094) ; NAGASHIMA Takeshi 東北大学, 医学系研究科, 助教 (80443000) ; SAIGUSA Daisuke 東北大学, 東北メディカル・メガバンク機構, 講師 (90545237) ; MATSUMOTO Mitsuyo 東北大学, 医学系研究科, 助教 (80400448) ; IGARASHI Kazuhiko 東北大学, 医学系研究科, 教授 (00250738)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: エピジェネティクス / SAM合成酵素 / ヒストンメチル化 / DNAメチル化

Outline of Final Research Achievements

Methionine adenosyltransferase (MAT) catalyzes S-adenosylmethionine (SAM) synthesis, which is utilized as a methyl donor in transmethylation reactions. MATII, a MAT isozyme, is composed of the catalytic α and regulatory β subunits. Both of the subunits are recruited to a subset of target genes of Bach1 and MafK to facilitate their repression. However, it has been unclear how the nuclear accumulation of MATII subunits is regulated. Using overexpression and bimolecular fluorescence complementation, we found that MATIIβ promoted the nuclear localization of the α subunit and that resulting heterooligomer was present predominantly in nuclear compartment. A single serine residue of α subunit was required for its interaction with β subunit and efficient nuclear accumulation.These results suggest that β subunit defines nulcear-specific MAT isozyme by facilitating nuclear import of its catalytic subunit.

Free Research Field

生化学・分子生物学