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Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2
- Source :
- Nucleic Acids Research, Nucleic Acids Res. 47, 9069-9086 (2019)
- Publication Year :
- 2019
- Publisher :
- Oxford University Press (OUP), 2019.
-
Abstract
- Pioneer transcription factors (PTF) can recognize their binding sites on nucleosomal DNA and trigger chromatin opening for recruitment of other non-pioneer transcription factors. However, critical properties of PTFs are still poorly understood, such as how these transcription factors selectively recognize cell type-specific binding sites and under which conditions can they can initiate chromatin remodelling. Here we show that early endoderm binding sites of the paradigm PTF Foxa2 are epigenetically primed by low levels of active chromatin modifications in embryonic stem cells (ESC). Priming of these binding sites is supported by preferential recruitment of Foxa2 to endoderm binding sites compared to lineage-inappropriate binding sites, when ectopically expressed in ESCs. We further show that binding of Foxa2 is required for chromatin opening during endoderm differentiation. However, increased chromatin accessibility was only detected on binding sites which are synergistically bound with other endoderm transcription factors. Thus, our data suggest that binding site selection of PTFs is directed by the chromatin environment and that chromatin opening requires collaboration of PTFs with additional transcription factors.
- Subjects :
- Cell
Biology
Histones
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Genetics
medicine
Animals
Histone code
Binding site
Transcription factor
reproductive and urinary physiology
030304 developmental biology
Mice, Knockout
Regulation of gene expression
0303 health sciences
Binding Sites
Models, Genetic
Endoderm
Gene regulation, Chromatin and Epigenetics
Gene Expression Regulation, Developmental
Cell Differentiation
Mouse Embryonic Stem Cells
Chromatin Assembly and Disassembly
Embryonic stem cell
Chromatin
ddc
GATA4 Transcription Factor
Cell biology
Histone Code
medicine.anatomical_structure
chemistry
embryonic structures
Hepatocyte Nuclear Factor 3-beta
FOXA2
030217 neurology & neurosurgery
DNA
Signal Transduction
Subjects
Details
- ISSN :
- 13624962 and 03051048
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- Nucleic Acids Research
- Accession number :
- edsair.doi.dedup.....c097438666027c10b6037b332e03b63d