Hepatocyte nuclear factor 1 alpha (HNF1A) regulates transcription of O‐GlcNAc transferase in a negative feedback mechanism. Issue 10 (14th May 2019)

• Record Type: Journal Article
• Authors: Zhang, Chuanhui; Xie, Fei; Li, Ling; Zhang, Cheng; Zhang, Yong; Ying, Wantao; Liu, Li; Yan, Xuli; Yin, Futao; Zhang, Lianwen
• Is Part Of: FEBS letters. Volume 593:Issue 10(2019)
• Page Start: 1050
• Page End: 1060
• Publication Date: 2019-05-14
• Subjects: HNF1A -- negative feedback mechanism -- OGT -- transcriptional regulation; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13381
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : O ‐GlcNAc transferase (OGT)‐catalyzed protein O‐GlcNAcylation is implicated in diverse cellular events. In the present study, we report the regulation of ogt transcription by the hepatocyte nuclear factor 1 homologue A (HNF1A) in HEK293T cells. We first identified a core ogt promoter (−150 to +200 bp) and confirmed its binding to the transcription factor HNF1A. We found that HNF1A regulates ogt transcription in a time‐dependent manner and that O‐GlcNAcylation of HNF1A represses ogt transcription. Electron‐transfer dissociation based tandem mass spectrometry analysis revealed 14 O ‐GlcNAc sites on HNF1A, six of which are predominantly modified, including Ser 303/304, Ser 471, Ser 560 and Thr 563/564 . We further found that loss of O‐GlcNAcylation at Ser 303/304 or Thr 563/564 significantly elevates ogt transcription. These findings highlight a negative feedback mechanism for ogt transcription, which partially explains the homeostasis of cellular O‐GlcNAcylation. Abstract :