Differential binding of erythroid Krupple-like factor to embryonic/fetal globin gene promoters during development.
The competition model for beta-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 have demonstrated, by chromatin immunoprecipitation, 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 3-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.
Zhou
Dewang
D
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama 35294, USA.
Pawlik
Kevin M
KM
Ren
Jinxiang
J
Sun
Chiao-Wang
CW
Townes
Tim M
TM
D000818:Animals; D047369:Chromatin Immunoprecipitation; D005319:Fetal Hemoglobin / Q000235:genetics*; D006579:Heterozygote; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic
D051741:Kruppel-Like Transcription Factors; C080774:erythroid Kruppel-like factor; D005319:Fetal Hemoglobin