TATA-Box Binding Protein O-GlcNAcylation at T114 Regulates Formation of the B-TFIID Complex and Is Critical for Metabolic Gene Regulation

Stéphan Hardivillé, Partha S. Banerjee, Ebru S. Selen Alpergin, Danielle M. Smith, Guanghui Han, Junfeng Ma, C. Conover Talbot, Ping Hu, Michael J. Wolfgang, Gerald W. Hart

Research output: Contribution to journalArticlepeer-review

Abstract

In eukaryotes, gene expression is performed by three RNA polymerases that are targeted to promoters by molecular complexes. A unique common factor, the TATA-box binding protein (TBP), is thought to serve as a platform to assemble pre-initiation complexes competent for transcription. Here, we describe a novel molecular mechanism of nutrient regulation of gene transcription by dynamic O-GlcNAcylation of TBP. We show that O-GlcNAcylation at T114 of TBP blocks its interaction with BTAF1, hence the formation of the B-TFIID complex, and its dynamic cycling on and off of DNA. Transcriptomic and metabolomic analyses of TBPT114A CRISPR/Cas9-edited cells showed that loss of O-GlcNAcylation at T114 increases TBP binding to BTAF1 and directly impacts expression of 408 genes. Lack of O-GlcNAcylation at T114 is associated with a striking reprogramming of cellular metabolism induced by a profound modification of the transcriptome, leading to gross alterations in lipid storage.

Original languageEnglish (US)
Pages (from-to)1143-1152.e7
JournalMolecular cell
Volume77
Issue number5
DOIs
StatePublished - Mar 5 2020

Keywords

  • B-TFIID
  • BTAF1
  • O-GlcNAc
  • O-GlcNAcylation
  • TATA-box binding protein
  • TBP
  • lipid droplets
  • metabolism
  • nutrient sensing
  • transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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