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Mol Cell. 2017 Dec 21;68(6):1067-1082.e12. doi: 10.1016/j.molcel.2017.11.026.

AP-1 Transcription Factors and the BAF Complex Mediate Signal-Dependent Enhancer Selection.

Author information

1
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. Electronic address: tvierbuchen@gmail.com.
2
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
3
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
4
Comprehensive Cancer Center and Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
#
Contributed equally

Abstract

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 ∼106 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.

KEYWORDS:

Ras/MAPK signaling; chromatin remodeling complexes; enhancers; genetics; genomics; growth factor signaling; lineage specification; mSWI/SNF (BAF) complexes; transcription factors; transcriptional regulation

PMID:
29272704
PMCID:
PMC5744881
DOI:
10.1016/j.molcel.2017.11.026
[Indexed for MEDLINE]
Free PMC Article

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