期刊
EMBO JOURNAL
卷 31, 期 22, 页码 4318-4333出版社
WILEY
DOI: 10.1038/emboj.2012.275
关键词
cell fate decisions; endothelial-haematopoietic transition; haematopoiesis; RUNX1; transcriptional programming of chromatin
资金
- BBSRC
- MRC
- European Community [LSHG-CT-2007-037445]
- NIH [NIH R01 CA118316, R01 HL112719]
- NIHR Cambridge Biomedical Research Centre
- Leukaemia & Lymphoma Research
- Cancer Research UK
- BBSRC [BB/I00050X/1, BB/I001220/1, BB/I001794/1, BB/I001220/2] Funding Source: UKRI
- MRC [G0901579, G0800784] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/I00050X/1, BB/I001220/1, BB/I001794/1, BB/I001220/2] Funding Source: researchfish
- Cancer Research UK [12765, 12486, 12487] Funding Source: researchfish
- Medical Research Council [G0800784B, G0800784, G0901579] Funding Source: researchfish
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [G0900729/1] Funding Source: researchfish
Cell fate decisions during haematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. To gain insight into how these transcription factors regulate the activation of haematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from haemogenic endothelium (HE) to haematopoietic progenitors. Using a Runx1 -/- embryonic stem cell differentiation model expressing an inducible Runx1 gene, we show that in the absence of RUNX1, haematopoietic genes bind SCL/TAL1, FLI1 and C/EBPb and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous de novo sites, initiating a local increase in histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of haematopoietic fate controlled by Runx1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing HE program but instead entails global reorganization of lineage-specific transcription factor assemblies. The EMBO Journal (2012) 31, 4318-4333. doi:10.1038/emboj.2012.275; Published online 12 October 2012
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