Repression of insulin gene transcription by indirect genomic signaling via the estrogen receptor in pancreatic beta cells.

ABSTRACT: The mechanism whereby 17β-estradiol (E2) mediates insulin gene transcription has not been fully elucidated. In this study, exposure of hamster insulinoma (HIT-T15) cells to 5 × 10^-9 to 1 × 10^-7 M E2 led to a concentration-dependent decrease of insulin mRNA levels. Transient expression of the estrogen receptor (ER) in HIT-T15 cells revealed that estrogen receptor α (ERα) repressed transcription of the rat insulin II promoter in both ligand-dependent and ligand-independent manners. The N-terminal A/B domain of ERα was not required for either activity. However, the repression was absent with mutated ER lacking the DNA-binding domain. Moreover, introducing mutations in the D-box and P-box of the zinc finger of ER (C227S, C202L) also abolished the repression. Deletion of t

SUBMITTER: Sekido T 

PROVIDER: S-EPMC6443913 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature