O-GlcNAc transferase is involved in glucocorticoid receptor-mediated transrepression

Min Dian Li, Hai Bin Ruan, Jay P. Singh, Lin Zhao, Tingting Zhao, Sascha Azarhoush, Jing Wu, Ronald M. Evans, Xiaoyong Yang

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Recruitment of O-GlcNAc transferase (OGT) to promoters plays an important role in gene repression. Glucocorticoid signaling represses the transcriptional activities of NF-κB and AP-1 through direct binding, yet the molecular mechanisms remain to be elucidated. Here we report that OGT is an important component of GR-mediated transrepression. OGT associates with ligand-bound GR in a multi-protein repression complex. Overexpression of OGT potentiates the GR transrepression pathway, whereas depletion of endogenous OGT by RNA interference abolishes the repression. The recruitment of OGT by GR leads to increased O-GlcNAcylation and decreased phosphorylation of RNA polymerase II on target genes. Functionally, overexpression of OGT enhances glucocorticoid-induced apoptosis in resistant cell lines while knockdown of OGT prevents sensitive cell lines from apoptosis. These studies identify a molecular mechanism of GR transrepression, and high-light the function of O-GlcNAc in hormone signaling.

Original languageEnglish (US)
Pages (from-to)12904-12912
Number of pages9
JournalJournal of Biological Chemistry
Issue number16
StatePublished - Apr 13 2012

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