FOXO1 transrepresses peroxisome proliferator-activated receptor gamma transactivation, coordinating an insulin-induced feed-forward response in adipocytes.

ABSTRACT: The transcriptional factor FoxO1 plays an important role in metabolic homeostasis. Herein we identify a novel transrepressional function that converts FoxO1 from an activator of transcription to a promoter-specific repressor of peroxisome proliferator-activated receptor gamma (PPARgamma) target genes that regulate adipocyte biology. FoxO1 transrepresses PPARgamma via direct protein-protein interactions; it is recruited to PPAR response elements (PPRE) on PPARgamma target genes by PPARgamma bound to PPRE and interferes with promoter DNA occupancy of the receptor. The FoxO1 transrepressional function, which is independent and dissectible from the transactivational effects, does not require a functional FoxO1 DNA binding domain, but dose require an evolutionally conserved 31 amino acids LXXLL

SUBMITTER: Fan W 

PROVIDER: S-EPMC2673287 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature