Interplay of m⁶A and H3K27 trimethylation restrains inflammation during bacterial infection.

ABSTRACT: While N ⁶-methyladenosine (m⁶A) is the most prevalent modification of eukaryotic messenger RNA (mRNA) involved in various cellular responses, its role in modulating bacteria-induced inflammatory response remains elusive. Here, we showed that loss of the m⁶A reader YTH-domain family 2 (YTHDF2) promoted demethylation of histone H3 lysine-27 trimethylation (H3K27me3), which led to enhanced production of proinflammatory cytokines and facilitated the deposition of m⁶A cotranscriptionally. Mechanistically, the mRNA of lysine demethylase 6B (KDM6B) was m⁶A-modified and its decay mediated by YTHDF2. YTHDF2 deficiency stabilized KDM6B to promote H3K27me3 demethylation of multiple proinflammatory cytokines and subsequ

SUBMITTER: Wu C 

PROVIDER: S-EPMC7438091 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature