Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
TATA-Box Binding Protein O-GlcNAcylation at T114 Regulates Formation of the B-TFIID Complex and Is Critical for Metabolic Gene Regulation.
Molecular Cell ( IF 14.5 ) Pub Date : 2019-12-19 , DOI: 10.1016/j.molcel.2019.11.022 Stéphan Hardivillé 1 , Partha S Banerjee 1 , Ebru S Selen Alpergin 1 , Danielle M Smith 1 , Guanghui Han 1 , Junfeng Ma 1 , C Conover Talbot 2 , Ping Hu 1 , Michael J Wolfgang 1 , Gerald W Hart 1
Molecular Cell ( IF 14.5 ) Pub Date : 2019-12-19 , DOI: 10.1016/j.molcel.2019.11.022 Stéphan Hardivillé 1 , Partha S Banerjee 1 , Ebru S Selen Alpergin 1 , Danielle M Smith 1 , Guanghui Han 1 , Junfeng Ma 1 , C Conover Talbot 2 , Ping Hu 1 , Michael J Wolfgang 1 , Gerald W Hart 1
Affiliation
|
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.
中文翻译：
TATA盒结合蛋白O-GlcNAcylation在T114处调节B-TFIID复合物的形成，对于代谢基因的调控至关重要。
在真核生物中，基因表达是通过分子复合物靶向启动子的三种RNA聚合酶进行的。TATA-box结合蛋白（TBP）是一个独特的共同因素，被认为是装配起转录作用的起始前复合物的平台。在这里，我们描述了通过TBP的动态O-GlcNAcylation营养调节基因转录的新型分子机制。我们显示，TBP的T114处的O-GlcNAcylation阻止了它与BTAF1的相互作用，因此形成了B-TFIID复合物，并且它动态地循环打开和关闭DNA。TBPT114A CRISPR / Cas9编辑的细胞的转录组和代谢组学分析表明，在T114处O-GlcNAcylation的丢失会增加TBP与BTAF1的结合，并直接影响408个基因的表达。
更新日期：2019-12-19
中文翻译：
TATA盒结合蛋白O-GlcNAcylation在T114处调节B-TFIID复合物的形成，对于代谢基因的调控至关重要。
在真核生物中，基因表达是通过分子复合物靶向启动子的三种RNA聚合酶进行的。TATA-box结合蛋白（TBP）是一个独特的共同因素，被认为是装配起转录作用的起始前复合物的平台。在这里，我们描述了通过TBP的动态O-GlcNAcylation营养调节基因转录的新型分子机制。我们显示，TBP的T114处的O-GlcNAcylation阻止了它与BTAF1的相互作用，因此形成了B-TFIID复合物，并且它动态地循环打开和关闭DNA。TBPT114A CRISPR / Cas9编辑的细胞的转录组和代谢组学分析表明，在T114处O-GlcNAcylation的丢失会增加TBP与BTAF1的结合，并直接影响408个基因的表达。
京公网安备 11010802027423号