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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4078-4083.
Prepublished online as a Blood First Edition Paper on February 5, 2004; DOI 10.1182/blood-2003-09-3231.
Submitted September 22, 2003
Accepted January 27, 2004
Regulatory elements of the EKLF gene that direct erythroid cell-specific expression during mammalian development
Li Xue, Xiaoyong Chen, Yanjie Chang, and James J Bieker*
Brookdale Department of Molecular, Cell & Developmental Biology, Mount Sinai School of Medicine, New York, NY, USA
* Corresponding author; email: james.bieker{at}mssm.edu.
Erythroid Kruppel-like Factor (EKLF) plays an essential role in enabling  -globin expression during erythroid ontogeny. It is first expressed in the extraembryonic mesoderm of the yolk sac within the blood islands, and then later within the hepatic primordia. We have used transgenic analyses to verify that 950 bp located adjacent to the EKLF start site of transcription are sufficient to generate lacZ expression within the blood islands as well as the fetal liver during embryonic development. Of particular importance are three regions, two of which overlap endogenous erythroid-specific DNase hypersensitive sites, and one of which includes the proximal promoter region. The onset of transgene expression mimics that of endogenous EKLF as it begins by d7.5-8.0. In addition, it exhibits a strict hematopoietic specificity, localized only to these cells and not to the adjacent vasculature at all stages examined. Finally, expression is heterocellular. These analyses demonstrate that a surprisingly small DNA segment contains all the information needed to target a linked gene to the hematopoietic compartment at both early and later stages of development, and may be a useful cassette for this purpose.
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