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

Stephan Hardiville, 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 journalArticle

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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