Dataset Information

Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2 gene locus.

ABSTRACT: MATII biosynthesizes AdoMet, which supplies methyl group for methylation of molecules, including histone.MATII interacts with histone methyltransferase SETDB1 and inhibits COX-2 gene expression.AdoMet synthesis and histone methylation are coupled on chromatin by a physical interaction of MATII and SETDB1 at the MafK target genes.MATII may be important for both gene-specific and epigenome-wide regulation of histone methylation. Methionine adenosyltransferase (MAT) synthesizes S-adenosylmethionine (AdoMet), which is utilized as a methyl donor in transmethylation reactions involving histones. MATII?, a MAT isozyme, serves as a transcriptional corepressor in the oxidative stress response and forms the AdoMet-integrating transcription regulation module, affecting histone methyltransferase activities. However, the identities of genes regulated by MATII? or its associated methyltransferases are unclear. We 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?.

SUBMITTER: Kera Y

PROVIDER: S-EPMC3650394 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2 gene locus.

Kera Yohei Y Katoh Yasutake Y Ohta Mineto M Matsumoto Mitsuyo M Takano-Yamamoto Teruko T Igarashi Kazuhiko K

The Journal of biological chemistry 20130328 19

<h4>Background</h4>MATII biosynthesizes AdoMet, which supplies methyl group for methylation of molecules, including histone.<h4>Results</h4>MATII interacts with histone methyltransferase SETDB1 and inhibits COX-2 gene expression.<h4>Conclusion</h4>AdoMet synthesis and histone methylation are coupled on chromatin by a physical interaction of MATII and SETDB1 at the MafK target genes.<h4>Significance</h4>MATII may be important for both gene-specific and epigenome-wide regulation of histone methyla ...[more]

PMID: 23539621

Similar Datasets

Project description:Histone post-translational modifications (PTMs) are associated with epigenetic states that form the basis for cell-type-specific gene expression1,2. Once established, histone PTMs can be maintained by positive feedback involving enzymes that recognize a pre-existing histone modification and catalyse the same modification on newly deposited histones. Recent studies suggest that in wild-type cells, histone PTM-based positive feedback is too weak to mediate epigenetic inheritance in the absence of other inputs3-7. RNA interference (RNAi)-mediated histone H3 lysine 9 methylation (H3K9me) and heterochromatin formation define a potential epigenetic inheritance mechanism in which positive feedback involving short interfering RNA (siRNA) amplification can be directly coupled to histone PTM positive feedback8-14. However, it is not known whether the coupling of these two feedback loops can maintain epigenetic silencing independently of DNA sequence and in the absence of enabling mutations that disrupt genome-wide chromatin structure or transcription15-17. Here, using the fission yeast Schizosaccharomyces pombe, we show that siRNA-induced H3K9me and silencing of a euchromatic gene can be epigenetically inherited in cis during multiple mitotic and meiotic cell divisions in wild-type cells. This inheritance involves the spreading of secondary siRNAs and H3K9me3 to the targeted gene and surrounding areas, and requires both RNAi and H3K9me, suggesting that the siRNA and H3K9me positive-feedback loops act synergistically to maintain silencing. By contrast, when maintained solely by histone PTM positive feedback, silencing is erased by H3K9 demethylation promoted by Epe1, or by interallelic interactions that occur after mating to cells containing an expressed allele even in the absence of Epe1. These findings demonstrate that the RNAi machinery can mediate transgenerational epigenetic inheritance independently of DNA sequence or enabling mutations, and reveal a role for the coupling of the siRNA and H3K9me positive-feedback loops in the protection of epigenetic alleles from erasure.

Dataset Information

Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2 gene locus.

Publications

Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2 gene locus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets