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pubmed:abstractText |
Enhancer elements modulate promoter activity over vast chromosomal distances, and mechanisms that ensure restrictive interactions between promoters and enhancers are critical for proper control of gene expression. The human beta-globin locus control region (LCR) activates expression of five genes in erythroid cells, including the proximal embryonic epsilon- and the distal adult beta-globin genes. To test for possible distance sensitivity of the genes to the LCR, we extended the distance between the LCR and genes by 2.3 kbp within the context of a yeast artificial chromosome, followed by the generation of transgenic mice (TgM). In these TgM lines, epsilon-globin gene expression decreased by 90%, while the more distantly located gamma- or beta-globin genes were not affected. Remarkably, introduction of a consensus EKLF binding site into the epsilon-globin promoter rendered its expression distance insensitive; when tested in an EKLF-null genetic background, expression of the mutant epsilon-globin gene was severely compromised. Thus, the epsilon-globin gene differs in its distance sensitivity to the LCR from the other beta-like globin genes, which is, at least in part, determined by the transcription factor EKLF.
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pubmed:affiliation |
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8577, Japan.
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