GSE59160 BRD4 links carbohydrate and lipid synthetic pathways to a core transcriptional network for a cell-type specific metabolic response (RNA-seq Liver)

Contributors : Sabina Benko ; Fan Zhang ; Blanca Andino ; Guangtao Zhang ; SiDe Li ; Virginia Gillespie ; Andrew C Shin ; Francesca Aguilo ; Chih-Hung Chen ; Weijia Zhang ; Christoph Buettner ; Ming-Ming Zhou ; Martin J WalshSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusGlucose and fat metabolism are tightly interconnected where endogenous de novo lipogenesis (DNL) serves to convert carbohydrates directly into lipids. Here, we explored the role of the long isoform Brd4 as a key transcriptional co-activator in lipogenesis. As a member of the Bromo-extraterminal (BET) protein family, Brd4 is characterized by two tandem bromodomains that bind acetylated lysine on both histone and non-histone proteins in chromatin. We found that treatment with MS417, a small molecule inhibitor of Brd4 binding to acetylated lysine, suppresses 3T3-L1 adipocyte differentiation. MS417-treated obese (ob/ob) mice displayed resistance to weight gain and loss of fat from steatotic livers. Comprehensive RNA-seq and ChIP-seq analyses delineate a Brd4-driven gene network required for glycolysis-lipogenesis flux that is shared between glycolytic liver and 3T3-L1 adipocytes, but absent in the non-glycolytic white abdominal fat. Our data further reveal that Brd4 functions to provide specific metabolic resources, such as acetyl-CoA and nicotinamide adenine dinucleotide (NAD) cofactors, in cell types utilizing DNL. Collectively, these findings provide a novel v...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research