Proteomics

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Pivotal role for S-nitrosylation of DNA methyltransferase in epigenetic regulation


ABSTRACT: DNMTs catalyze the methylation of cytosine with SAM. DNA methylation affects key cellular processes by regulating gene expression, thus serving a variety of physiological and pathophysiological roles. However, the chemical mechanisms of DNA methylation by which its enzymatic activity is regulated have not been fully elucidated. We found that a critical cysteine residue in DNMT is the target of protein S-nitrosylation, leading to the attenuation of DNMT enzymatic activity and consequent aberrant regulation of gene expression during neoplastic cell proliferation. Our results demonstrate that de novo DNA methylation mediated by DNMT3 is regulated by NO, which is involved in tumor formation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Akihiro Ito  

LAB HEAD: Akihiro Ito

PROVIDER: PXD039437 | Pride | 2023-03-11

REPOSITORIES: Pride

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Publications


DNA methyltransferases (DNMTs) catalyze methylation at the C5 position of cytosine with S-adenosyl-L-methionine. Methylation regulates gene expression, serving a variety of physiological and pathophysiological roles. The chemical mechanisms regulating DNMT enzymatic activity, however, are not fully elucidated. Here, we show that protein S-nitrosylation of a cysteine residue in DNMT3B attenuates DNMT3B enzymatic activity and consequent aberrant upregulation of gene expression. These genes include  ...[more]

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