XLID syndrome gene Med12 promotes Ig isotype switching through chromatin modification and enhancer RNA regulation

ABSTRACT: The transcriptional coactivator Med12 regulates gene expression through its kinase module. Here, we show a kinase module–independent function of Med12 in CSR. Med12 is essential for super-enhancer activation by collaborating with p300-Jmjd6/Carm1 coactivator complexes. Med12 loss decreases H3K27 acetylation and eRNA transcription with concomitant impairment of AID-induced DNA breaks, S-S synapse formation, and 3′RR-Eμ interaction. CRISPR-dCas9–mediated enhancer activation reestablishes the epigenomic and transcriptional hallmarks of the super-enhancer and fully restores the Med12 depletion defects. Moreover, 3′RR-derived eRNAs are critical for promoting S region epigenetic regulation, synapse formation, and recruitment of Med12 and AID to the IgH locus. We find that XLID syndrome–associate

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PROVIDER: S-EPMC9699684 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature