Retinoic acid inhibits white adipogenesis by disrupting GADD45A-mediated Zfp423 DNA demethylation.

ABSTRACT: Retinoic acid (RA), a bioactive metabolite of vitamin A, is a critical mediator of cell differentiation. RA blocks adipogenesis, but mechanisms remain to be established. ZFP423 is a key transcription factor maintaining white adipose identity. We found that RA inhibits Zfp423 expression and adipogenesis via blocking DNA demethylation in the promoter of Zfp423, a process mediated by growth arrest and DNA-damage-inducible protein alpha (GADD45A). RA induces the partnering between retinoic acid receptor (RAR) and tumor suppressor inhibitor of growth protein 1 (ING1), which prevents the formation of GADD45A and ING1 complex necessary for locus-specific Zfp423 DNA demethylation. In vivo, vitamin A supplementation prevents obesity, downregulates Gadd45a expression, and reduces GADD45A binding and

SUBMITTER: Wang B 

PROVIDER: S-EPMC6080365 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature