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A more recent version of this article appeared on June 9, 2006
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M601182200v1
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Papers In Press, published online ahead of print April 10, 2006
J. Biol. Chem, 10.1074/jbc.M601182200
Submitted on February 7, 2006
Revised on April 10, 2006
Accepted on April 10, 2006

Differential binding of EKLF to embryonic/fetal globin gene promoters during development

Dewang Zhou, Kevin M. Pawlik, Jinxiang Ren, Chiao-Wang Sun, and Tim M. Townes

Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294

Corresponding Author: ttownes{at}uab.edu

The competition model for ß-like globin gene switching during development predicts that differential binding of transcription factors to globin gene promoters and/or proximal enhancers regulate the competitive interactions of globin gene family members with the powerful Locus Control Region (LCR). Direct interactions of individual genes with the LCR are essential for high-level expression in erythroid cells. In this paper we demonstrate by chromatin immunoprecipitation (ChIP) that Erythroid Krupple-like Factor (EKLF) binds to embryonic/fetal globin gene promoters in primitive but not in definitive erythroid cells. EKLF binds strongly to adult globin gene promoters and to LCR sequences HS4, HS3, HS2 and HS1 in both primitive and definitive erythroid cells. Trimethylation of histone H3K4 and H3K27 at the embryonic/fetal and adult globin gene promoters is equivalent in definitive cells; therefore, the differential binding of EKLF to these promoters does not appear to result from changes in chromatin configuration. Interestingly, the level of EKLF in definitive cells is three-fold higher than the level in primitive cells. These results suggest that temporal-specific changes in EKLF abundance result in differential binding of this essential, erythroid transcription factor to embryonic/fetal globin gene promoters during development and that these changes in EKLF binding specificity mediate the competitive interactions of globin gene family members with the LCR.


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