GSE42474
Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes [ChIP-Seq and RNA-seq]
The master transcription factors Oct4, Sox2 and Nanog bind enhancer elements and recruit the Mediator co-activator to activate much of the gene expression program of embryonic stem cells (ESCs).  We report here that these ESC master transcription factors and Mediator form “super-enhancers” at most genes that are known to control the pluripotent state, including those encoding the master transcription factors themselves. These super-enhancers consist of extraordinarily large genomic domains occupied by exceptional amounts of Oct4 and Mediator.  Super-enhancers stimulate considerably higher transcription than typical enhancers in reporter vectors.  ESC differentiation causes preferential loss of expression of super-enhancer -associated genes.  Super-enhancers are also found at key cell identity genes in differentiated cells. These results implicate super-enhancers in the control of mammalian cell identity and differentiation and suggest that these elements might generally be used to identify genes that control cell-type specific gene expression programs in many mammalian cells. Overall design: ChIP-Seq and RNA-seq of Med1 in ZHBTc4 ES during treatment with doxycycline. ChIP-Seq data of Med1 in 38B9 pro-B cells.