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| Status |
Public on Oct 18, 2012 |
| Title |
RUNX1 reshapes the epigenetic landscape at the onset of hematopoiesis |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Cell fate decisions during hematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. In order to gain insight about how these transcription factors regulate the activation of hematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from hemogenic endothelium to hematopoietic progenitors. Using a RUNX1-/- embryonic stem cell differentiation model expressing an inducible RUNX1 gene, we show that in the absence of RUNX1, SCL/TAL1, FLI1 and C/EBPβ prime hematopoietic genes 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 new sites, initiating a local increase of histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of hematopoietic fate controlled by RUNX1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing hemogenic endothelium program but instead entails global reorganization of lineage-specific transcription factor assemblies.
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| Overall design |
ChIPseq data from transcription factors Runx1, Fli-1, Scl/Tal1 and C/EBPβ, histone modification H3K9Ac as well as RNA Pol II obtained from differentiating murine hematopoietic cells
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| Contributor(s) |
Lichtinger M, Ingram R, Hannah R, Müller D, Clarke D, Assi SA, Lie-A-Ling M, Noailles L, Vijayabaskar M, Wu M, Tenen DG, Westhead DR, Kouskoff V, Lacaud G, Göttgens B, Bonifer C |
| Citation(s) |
23064151 |
| Submission date |
Aug 20, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Rebecca Louise Hannah |
| E-mail(s) |
rlh60@cam.ac.uk, rebeccahannah@live.co.uk
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| Organization name |
University of Cambridge
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| Department |
Haematology
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| Street address |
Addenbrookes Hospital, Hills Road
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0XY |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA173414 |
| SRA |
SRP014971 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE40235_RAW.tar |
3.8 Gb |
(http)(custom) |
TAR (of BED, BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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