FOXD3 Regulates Pluripotent Stem Cell Potential by Simultaneously Initiating and Repressing Enhancer Activity.
Cell Stem Cell
; 18(1): 104-17, 2016 Jan 07.
Article
in En
| MEDLINE
| ID: mdl-26748757
ABSTRACT
Early development is governed by the ability of pluripotent cells to retain the full range of developmental potential and respond accurately to developmental cues. This property is achieved in large part by the temporal and contextual regulation of gene expression by enhancers. Here, we evaluated regulation of enhancer activity during differentiation of embryonic stem to epiblast cells and uncovered the forkhead transcription factor FOXD3 as a major regulator of the developmental potential of both pluripotent states. FOXD3 bound to distinct sites in the two cell types priming enhancers through a dual-functional mechanism. It recruited the SWI/SNF chromatin remodeling complex ATPase BRG1 to promote nucleosome removal while concurrently inhibiting maximal activation of the same enhancers by recruiting histone deacetylases1/2. Thus, FOXD3 prepares cognate genes for future maximal expression by establishing and simultaneously repressing enhancer activity. Through switching of target sites, FOXD3 modulates the developmental potential of pluripotent cells as they differentiate.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Transcription Factors
/
Nuclear Proteins
/
Gene Expression Regulation
/
Enhancer Elements, Genetic
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DNA Helicases
/
Pluripotent Stem Cells
/
Forkhead Transcription Factors
Limits:
Animals
Language:
En
Journal:
Cell Stem Cell
Year:
2016
Document type:
Article
Affiliation country:
United States