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Hepatocyte nuclear factor 1 alpha (HNF1A) regulates transcription of O ‐GlcNAc transferase in a negative feedback mechanism
Author(s) -
Zhang Chuanhui,
Xie Fei,
Li Ling,
Zhang Cheng,
Zhang Yong,
Ying Wantao,
Liu Li,
Yan Xuli,
Yin Futao,
Zhang Lianwen
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13381
Subject(s) - hepatocyte nuclear factors , transcription factor , transcription (linguistics) , chemistry , microbiology and biotechnology , transferase , hek 293 cells , biology , biochemistry , gene , enzyme , linguistics , philosophy
O ‐Glc NA c transferase ( OGT )‐catalyzed protein O‐Glc NA cylation 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 ( HNF 1A) in HEK 293T cells. We first identified a core ogt promoter (−150 to +200 bp) and confirmed its binding to the transcription factor HNF 1A. We found that HNF 1A regulates ogt transcription in a time‐dependent manner and that O‐Glc NA cylation of HNF 1A represses ogt transcription. Electron‐transfer dissociation based tandem mass spectrometry analysis revealed 14 O ‐Glc NA c sites on HNF 1A, 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‐Glc NA cylation 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‐Glc NA cylation.