An emerging role for bromodomain-containing proteins in chromatin regulation and transcriptional control of adipogenesis

Abstract 

Transcriptional co-activators, co-repressors and chromatin remodeling machines are essential elements in the transcriptional programs directed by the master adipogenic transcription factor PPARγ. Many of these components have orthologs in other organisms, where they play roles in development and pattern formation, suggesting new links between cell fate decision-making and adipogenesis. This review focuses on bromodomain-containing protein complexes recently shown to play a critical role in adipogenesis. Deeper understanding of these pathways is likely to have major impact on treatment of obesity-associated diseases, including metabolic syndrome, cardiovascular disease and Type 2 diabetes. The research effort is urgent because the obesity epidemic is serious; the medical community is ill prepared to cope with the anticipated excess morbidity and mortality associated with diet-induced obesity.

Abbreviations: BAF, BRM/BRG1-associated factors, BAT, brown adipose tissue, BET, bromodomain and extraterminal domain, BMP, bone morphogenetic proteins, BRG1, brahma-related gene 1, BRM, brahma, CBP, CREB (cyclic AMP-responsive element binding) binding protein, C/EBP, CCAAT/enhancer binding protein, ChIP, chromatin immunoprecipitation, co-IP, co-immunoprecipitation, CVD, cardiovascular disease, HAT, histone acetyltransferase, HDAC, histone deacetylase, MHO, metabolically healthy obese, P/CAF, p300/CBP-associated factor, PPARγ, peroxisome proliferator-activated receptor γ, PPRE, PPAR-responsive element, RB, retinoblastoma protein, RXR, retinoid X receptor, SMRT, silencing mediator of retinoid and thyroid hormone receptors, SWI/SNF, switch mating type/sucrose non-fermenting, TAF, TBP (TATA box binding protein)-associated factors, TRAP, thyroid hormone receptor-associated protein, TZD, thiazolidinedione, T2D, Type 2 diabetes, WAT, white adipose tissue

Keywords: Brd2, Switch mating type/sucrose non-fermenting, Peroxisome proliferator-activated receptor γ, Mouse model, Obesity