Methionine Adenosyltransferase II Serves as a Transcriptional Corepressor of Maf Oncoprotein

• DOI: 10.1016/j.molcel.2011.02.018
• Publication Date: 2011-03-07T22:46:47Z
• Authors: Yasutake Katoh; Tsuyoshi Ikura; Yutaka Hoshikawa; Satoshi Tashiro; Takashi Ito; Mineto Ohta; Yohei Kera; Tetsuo Noda; Kazuhiko Igarashi
• Keywords: Corepressor; Methionine Adenosyltransferase

Protein methylation pathways comprise methionine adenosyltransferase (MAT), which produces S-adenosylmethionine (SAM) and SAM-dependent substrate-specific methyltransferases. However, the function of MAT in the nucleus is largely unknown. MafK represses or activates expression of heme oxygenase-1 (HO-1) gene, depending on its heterodimer partners. Proteomics analysis of MafK revealed its interaction with MATIIα, a MAT isozyme. MATIIα was localized in nuclei and found to form a dense network with chromatin-related proteins including Swi/Snf and NuRD complexes. MATIIα was recruited to Maf recognition element (MARE) at HO-1 gene. When MATIIα was knocked down in murine hepatoma cell line, expression of HO-1 was derepressed at both basal and induced levels. The catalytic activity of MATIIα, as well as its interacting factors such as MATIIβ, BAF53a, CHD4, and PARP1, was required for HO-1 repression. MATII serves as a transcriptional corepressor of MafK by interacting with chromatin regulators and supplying SAM for methyltransferases.