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| Status |
Public on Jul 27, 2019 |
| Title |
CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Knockdown of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation in a cell autonomous manner in the embryo and adult. We performed ChIP sequencing to determine the genomic localization of CHD7 in human CD34+ and mouse HSPCs, revealing enrichment of binding motifs for hematopoietic transcription factors including Runx1 and GATA factors. CHD7 occupied regions are transcriptionally active and are near genes with hematopoietic function. Decreased Runx1 occupancy correlated with loss of CHD7 occupancy. Together, the physical and genetic interaction data support a model in which CHD7 interacts with and modulates Runx1 activity to provide proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults. This represents a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.
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| |
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| Overall design |
Analysis of CHD7 and RUNX1 binding in CBFV-MYH11 expressing hematopoietic progenitor cells, in replicate.
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| |
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| Contributor(s) |
Wilson NK, Moignard V, Calero Nieto F |
| Citation(s) |
32883883 |
| |
| Submission date |
Jul 01, 2016 |
| Last update date |
Apr 04, 2023 |
| Contact name |
Evangelia Diamanti |
| E-mail(s) |
ed347@cam.ac.uk
|
| Phone |
01223 62317
|
| Organization name |
University of Cambridge
|
| Department |
Haematology
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| Lab |
Gottgens
|
| Street address |
Wellcome Trust / MRC Building, Hills Road
|
| City |
Cambridge |
| ZIP/Postal code |
CB2 0XY |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA328994 |
| SRA |
SRP093468 |
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