![]() ![]() These results indicate that super-enhancers drive genes that are essential for cell identity in many mammalian cell types. Super-enhancers were found in a wide variety of differentiated cell types, again associated with key cell-type-specific genes known to play prominent roles in control of their gene expression program. These large domains, or super-enhancers, were found to contain high levels of the key ESC transcription factors Oct4, Sox2, Nanog, Klf4, and Esrrb to stimulate higher transcriptional activity than typical enhancers and to be exceptionally sensitive to reduced levels of Mediator. We found that much of enhancer-associated Mediator occupies exceptionally large enhancer domains and that these domains are associated with genes that play prominent roles in ESC biology. Interest in further understanding the importance of Mediator in ESCs led us to further investigate enhancers bound by the master transcription factors and Mediator in these cells. Super-enhancers thus play key roles in the control of mammalian cell identity. In other more differentiated cells, super-enhancers containing cell-type-specific master transcription factors are also found at genes that define cell identity. ![]() Reduced levels of Oct4 or Mediator cause preferential loss of expression of super-enhancer-associated genes relative to other genes, suggesting how changes in gene expression programs might be accomplished during development. Super-enhancers differ from typical enhancers in size, transcription factor density and content, ability to activate transcription, and sensitivity to perturbation. These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator. We report here that the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state. Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs).
0 Comments
Leave a Reply. |