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Dynamic Interactions of TATA‐Box Binding Protein with Promoters is Regulated by O‐GlcNAcylation
Author(s) -
Hardivillé Stéphan,
Han Guanghui,
Ma Junfeng,
Hu Ping,
Banerjee Partha S.,
Hart Gerald W.
Publication year - 2016
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.30.1_supplement.617.1
Subject(s) - microbiology and biotechnology , chromatin , tata box binding protein , tata binding protein , rna polymerase ii , chemistry , transcription (linguistics) , transcription factor ii a , transcription preinitiation complex , chromatin immunoprecipitation , transcription factor , promoter , dna , biology , biochemistry , dna binding protein , gene , gene expression , linguistics , philosophy
O‐GlcNAcylation is a dynamic posttranslational modification tightly correlated to the concentration of UDP‐GlcNAc, the end product of the hexosamine biosynthetic pathway (HBP), which varies according nutritional factors. Through HBP activity and production of UDP‐GlcNAc, OGT senses nutrient availability and forward the signal to downstream effectors by transferring a GlcNAc moiety to the targeted proteins. In return, the O ‐GlcNAcase resets the signal. Interestingly, literature points out a regulation of the basal transcription machinery by O‐GlcNAc. 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 (PIC). 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. Here, we mapped tree O‐GlcNAc sites on the N‐terminus domain of TBP (T114, T126 and S158), and shown that O‐GlcNAc inhibitor/activator affect localization of TBP with specific chromatin marks. O‐GlcNAcylated TBP is bound to DNA and the sugar inhibits the interaction with BTAF1. TBP site‐specific O‐GlcNAc mutants have been used to point out the T114 as the main regulator of its 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 of TBP at T114 regulates TBP/BTAF1 dynamics on gene promoters.