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Nucleic Acids Res. 2019 Sep 26;47(17):9069-9086. doi: 10.1093/nar/gkz627.

Pre-marked chromatin and transcription factor co-binding shape the pioneering activity of Foxa2.

Author information

1
Division of Molecular Biology, Biomedical Center, Faculty of Medicine, LMU Munich, Germany.
2
Helmholtz Zentrum München, Institute of Stem Cell Research, Neuherberg, Germany.
3
Helmholtz Zentrum München, Institute of Diabetes and Regeneration Research, Neuherberg, Germany.
4
Bioinformatic Core Facility, Biomedical Center, LMU Munich, Martinsried, Germany.
5
Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway.
6
German Center for Diabetes Research (DZD), Neuherberg, Germany.
7
Technische Universität München, Germany.
8
Munich Center for Integrated Protein Science (CiPSM), Munich, Germany.

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 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.

PMID:
31350899
PMCID:
PMC6753583
DOI:
10.1093/nar/gkz627
[Indexed for MEDLINE]
Free PMC Article

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