Specific ablation of the NCoR corepressor δ splice variant reveals alternative RNA splicing as a key regulator of hepatic metabolism.

ABSTRACT: The NCoR corepressor plays critical roles in mediating transcriptional repression by both nuclear receptors and non-receptor transcription factors. Alternative mRNA splicing of NCoR produces a series of variants with differing molecular and biological properties. The NCoRω splice-variant inhibits adipogenesis whereas the NCoRδ splice-variant promotes it, and mice bearing a splice-specific knockout of NCoRω display enhanced hepatic steatosis and overall weight gain on a high fat diet as well as a greatly increased resistance to diet-induced glucose intolerance. We report here that the reciprocal NCoRδ splice-specific knock-out mice display the contrary phenotypes of reduced hepatic steatosis and reduced weight gain relative to the NCoRω-/- mice. The NCoRδ-/- mice also fail to demonstrate th

SUBMITTER: Goodson ML 

PROVIDER: S-EPMC7588069 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature