Non-canonical function of histone methyltransferase G9a in the translational regulation of chronic inflammation.

ABSTRACT: We report a novel translation-regulatory function of G9a, a histone methyltransferase and well-understood transcriptional repressor, in promoting hyperinflammation and lymphopenia; two hallmarks of endotoxin tolerance (ET)-associated chronic inflammatory complications. Using multiple approaches, we demonstrate that G9a interacts with multiple translation regulators during ET, particularly the N6-methyladenosine (m⁶A) RNA methyltransferase METTL3, to co-upregulate expression of certain m⁶A-modified mRNAs that encode immune-checkpoint and anti-inflammatory proteins. Mechanistically, G9a promotes m⁶A methyltransferase activity of METTL3 at translational/post-translational level by regulating its expression, its methylation, and its cytosolic localization durin

SUBMITTER: Muneer A 

PROVIDER: S-EPMC11095832 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature