Journal
MOLECULAR CELL
Volume 77, Issue 5, Pages 1143-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2019.11.022
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Funding
- NIH [R01GM116891, R01DK61671, P01HL107153, R01NS072241, R01DK116746]
- Region Hauts-de-France
- GEFLUC award
- NHLBI [P01HL107153]
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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 TBPT(114)A 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.
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