"Regulating Energy and Lipid Metabolism through Pluripotent Transcriptional Networks"
Martin J. Walsh, PhD
Associate Professor, Structural and Chemical Biology
Associate Professor, Pediatrics, Hepatology
Associate Professor, Genetics and Genomic Sciences
Mt. Sinai School of Medicine
Glycolysis and lipid biosynthesis are crucial to stem cell behavior, but we know little about the transcriptional regulation of factors driving metabolism in concert with stem cell fate. We demonstrate through use of selective BET-bromodomain inhibitors, and comprehensive RNA-seq and ChIP-seq analysis in mouse embryonic stem cells (ESCs), that Brd4, a master chromatin reader, governs transcription of the core pluripotency network and genes required for lipogenesis. Our studies now show that Brd4 governs glycolysis and lipogenesis at the core of the pluripotency framework of genes and that Brd4 regulates critical nodes of metabolism leading to the production of co-factors needed for modifying the epigenome.