Journal
MOLECULAR CELL
Volume 68, Issue 6, Pages 1067-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2017.11.026
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Funding
- NIH [4R37NS028829-28]
- Damon Runyon Cancer Research Foundation [DRG2177-14]
- National Science Foundation [DGE0946799, DGE1144152]
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Enhancer elements are genomic regulatory sequences that direct the selective expression of genes so that genetically identical cells can differentiate and acquire the highly specialized forms and functions required to build a functioning animal. To differentiate, cells must select from among the similar to 10(6) enhancers encoded in the genome the thousands of enhancers that drive the gene programs that impart their distinct features. We used a genetic approach to identify transcription factors (TFs) required for enhancer selection in fibroblasts. This revealed that the broadly expressed, growth-factor-inducible TFs FOS/JUN (AP-1) play a central role in enhancer selection. FOS/JUN selects enhancers together with cell-type-specific TFs by collaboratively binding to nucleosomal enhancers and recruiting the SWI/SNF (BAF) chromatin remodeling complex to establish accessible chromatin. These experiments demonstrate how environmental signals acting via FOS/JUN and BAF coordinate with cell-type-specific TFs to select enhancer repertoires that enable differentiation during development.
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