The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis.
Affiliation
Cancer Research UK Stem Cell Biology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, United Kingdom.Issue Date
2009-12-17
Metadata
Show full item recordAbstract
The transcription factor RUNX1/AML1 is a master regulator of hematopoietic development. Its spatiotemporal expression is tightly regulated during embryonic development and is under the control of 2 alternative promoters, distal and proximal. Despite the functional significance of Runx1, the relative and specific activities of these 2 promoters remain largely uncharacterized. To investigate these activities, we introduced 2 reporter genes under the control of the proximal and distal promoters in embryonic stem cell and transgenic mouse lines. Our study reveals that both in vitro and in vivo the proximal Runx1 isoform marks a hemogenic endothelium cell population, whereas the subsequent expression of distal Runx1 defines fully committed definitive hematopoietic progenitors. Interestingly, hematopoietic commitment in distal Runx1 knockout embryos appears normal. Altogether, our data demonstrate that the differential activities of the 2 Runx1 promoters define milestones of hematopoietic development and suggest that the proximal isoform plays a critical role in the generation of hematopoietic cells from hemogenic endothelium. Identification and access to the discrete stages of hematopoietic development defined by the activities of the Runx1 promoters will provide the opportunity to further explore the cellular and molecular mechanisms of hematopoietic development.Citation
The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis. 2009, 114 (26):5279-89 BloodJournal
BloodDOI
10.1182/blood-2009-05-222307PubMed ID
19858498Language
enISSN
1528-0020ae974a485f413a2113503eed53cd6c53
10.1182/blood-2009-05-222307
Scopus Count
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