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O-linked β-N-acetylglucosamine transferase is involved in pro-opiomelanocortin gene expression in mouse pituitary corticotroph AtT-20 cells

Authors :
Koshi Makita
Mari Usutani
Makoto Daimon
Shinobu Takayasu
Yuki Nakada-Nakayama
Akira Sugawara
Kazunori Kageyama
Source :
Neuroscience Letters. 711:134407
Publication Year :
2019
Publisher :
Elsevier BV, 2019.

Abstract

Glucocorticoids and glucocorticoid receptors (GRs) suppress pituitary pro-opiomelanocortin (Pomc) gene expression. O-linked β-N-acetylglucosamine (O-GlcNAc) modification, mediated by O-GlcNAc transferase (OGT), plays an important role during gene transcription. However, whether OGT is involved in the GR-mediated transrepression that occurs in pituitary corticotroph cells is currently unknown. Here, we report that OGT regulates Pomc expression in the mouse corticotroph cell line AtT-20. The overexpression of OGT has an additive effect on the GR-mediated negative transcription pathway. Both the knockdown of OGT by RNA interference and the use of a chemical OGT inhibitor abolished the repressive effects of Pomc expression induced by GRs. OGT inhibition leads to both the decreased recruitment of GRs and the increased recruitment of RNA polymerase II to the Pomc locus. O-GlcNAc modification is involved in the negative regulation of Pomc transcription in corticotroph cells. OGT may be a promising therapeutic target for the treatment of Cushing's disease.

Details

ISSN :
03043940
Volume :
711
Database :
OpenAIRE
Journal :
Neuroscience Letters
Accession number :
edsair.doi.dedup.....2d6ea38a3938d37f5916e804147ed6c8
Full Text :
https://doi.org/10.1016/j.neulet.2019.134407