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Title

The scl +18/19 Stem Cell Enhancer Is Not Required for Hematopoiesis: Identification of a 5' Bifunctional Hematopoietic-Endothelial Enhancer Bound by Fli-1 and Elf-1

AuthorsGöttgens, Berthold; Broccardo, Cyril; Sánchez, María José ; 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.
KeywordsBasic Helix-Loop-Helix Transcription Factors
Cell lineage
DNA-binding proteins
ELF1 protein
Hematopoiesis
Nuclear proteins
Proto-oncogene proteins
Trans-activators
Issue DateMar-2004
PublisherAmerican Society for Microbiology
CitationMolecular and Cellular Biology 24(5): 1870-1883 (2004)
AbstractAnalysis 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.
Description13 páginas, 6 figuras.
Publisher version (URL)http://dx.doi.org/10.1128/MCB.24.5.1870-1883.2004
URIhttp://hdl.handle.net/10261/41001
DOI10.1128/MCB.24.5.1870-1883.2004
ISSN0270-7306
E-ISSN1098-5549
Appears in Collections:(CABD) Artículos
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