In primitive erythroid cells of human β-globin locus transgenic mice (TgM), the locus control region (LCR)-proximal ε- and γ-globin genes are transcribed, whereas the distal δ- and β-globin genes are silent. It is generally accepted that the β-globin gene is competitively suppressed by γ-globin gene expression at this developmental stage. Previously, however, we observed that ε-globin gene expression was severely attenuated when its distance from the LCR was extended, implying that β-globin gene might also be silenced because of its great distance from the LCR. Here, to clarify the β-globin gene silencing mechanism, we established TgM lines carrying either γ- or ε- plus γ-globin promoter deletions, without significantly altering the distance between the β-globin gene and the LCR. Precocious expression of δ- and β-globin genes was observed in primitive erythroid cells of mutant, but not wild-type TgM, which was most evident when both the ε and γ promoters were deleted. Thus, we clearly demonstrated that the repression of the δ- and β-globin genes in primitive erythroid cells is dominated by competitive silencing by the ε- and γ-globin gene promoters, and that ε- and the other β-like globin genes might be activated by two distinct mechanisms by the LCR.—Okamura, E., Matsuzaki, H., Campbell, A. D., Engel, J. D., Fukamizu, A., Tanimoto, K. All of the human β-type globin genes compete for LCR enhancer activity in embryonic erythroid cells of yeast artificial chromosome transgenic mice.
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All of the human β-type globin genes compete for LCR enhancer activity in embryonic erythroid cells of yeast artificial chromosome transgenic mice
Okamura, Eiichi; Matsuzaki, Hitomi; Campbell, Andrew D.; Engel, James Douglas; Fukamizu, Akiyoshi; Tanimoto, Keiji
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, Volume 23 (12): 4335
Fed of American Socs for Experimental Biology – Dec 1, 2009
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