Autor: |
Göttgens, Berthold, Broccardo, Cyril, Sanchez, Maria-Jose, Deveaux, Sophie, Murphy, George, Göthert, Joachim R., Kotsopoulou, Ekaterini, Kinston, Sarah, Delaney, Liz, Piltz, Sandie, Barton, Linda M., Knezevic, Kathy, Erber, Wendy N., Begley, C. Glenn, Frampton, Jonathan, Green, Anthony R. |
Předmět: |
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Zdroj: |
Molecular & Cellular Biology; Mar2004, Vol. 24 Issue 5, p1870-1883, 14p |
Abstrakt: |
Analysis of cis-regulatory elements is central to understanding the genomic program for development. The scl/tal-1 transcription factor is essential for lineage commitment to blood cell formation and previous studies identified an scl enhancer (the + 18/19 element) which was sufficient to target the vast majority of hematopoietic stem cells, together with hematopoietic progenitors and endothelium. Moreover, expression of scl under control of the + 18/19 enhancer rescued blood progenitor formation in scl-/- embryos. However, here we demonstrate by using a knockout approach that, within the endogenous scl locus, the + 18/19 enhancer is not necessary for the initiation of scl transcription or for the formation of hematopoietic cells. These results led to the identification of a bifunctional 5' enhancer (-3.8 element), which targets expression to hematopoietic progenitors and endothelium, contains conserved critical Ets sites, and is bound by Ets family transcription factors, including Fli-1 and Elf-1. These data demonstrate that two geographically distinct but functionally related enhancers regulate scl transcription in hematopoietic progenitors and endothelial cells and suggest that enhancers with dual hematopoietic-endothelial activity may represent a general strategy for regulating blood and endothelial development. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
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