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Nutrient regulation of TATA‐Box binding protein by O‐GlcNAcylation
Author(s) -
Hardiville Stephan,
Han Guanghui,
Ma Junfeng,
Hu Ping,
Banerjee Partha S.,
Hart Gerald W.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.908.7
Subject(s) - microbiology and biotechnology , tata box binding protein , chemistry , transcription (linguistics) , rna polymerase ii , promoter , chromatin , tata binding protein , transcription factor ii a , dna , transcriptional regulation , transcription factor , biochemistry , biology , dna binding protein , gene , gene expression , linguistics , philosophy
O‐GlcNAcylation is a dynamic post‐translational modification that is responsive to nutrient avabilality via the hexosamine biosynthetic pathway and its endproduct UDP‐GlcNAc. O‐GlcNAcylation serves as a nutrient sensor to regulate the activities of many proteins involved in nearly all biological processes. Interestingly, literature points out a regulation of the basal transcription machinery by O‐GlcNAcylation. TATA‐box binding protein (TBP) is a key player in regulating transcription since it is required for the activity of all three RNA polymerases. DNA‐bound TBP acts as a dock for recruitment of basal transcription factors and the RNA polymerase II to formation of a functional pre‐initiation complex. DNA‐bound TBP can also be recognized by NC2 and BTAF1. NC2 stabilizes the chromatin interaction of TBP, whereas the association of TBP with BTAF1 promotes its release upon hydrolysis of ATP. Here, we have shown that O‐GlcNAcylated TBP is bound to DNA, and that the sugar inhibits the interaction with BTAF1. Three O‐GlcNAc sites on the N‐terminus domain of TBP have been revealed by mass spectrometry. Site‐specific O‐GlcNAc mutants have been used to point out the T114 as the main regulator of TBP/BTAF1 interaction. Owing to the fact that BTAF1 dynamically regulates the chromatin interaction of TBP, we investigated the dynamic behavior of TBP and TBP O‐GlcNAc by Strip‐FRAP and ChIP assays. Collectively, our results indicate that O‐GlcNAcylation at T114 regulates TBP dynamics on gene promoters. Support or Funding Information The authors are supported by R01DK61671 and P01HL107153. G.W.H. receives a share of royalties received by Johns Hopkins University on sales of the CTD110.6 antibody, which is managed by JHU.