ENHANCER-DEPENDENT TRANSCRIPTION OF THE EPSILON-GLOBIN PROMOTER REQUIRES PROMOTER-BOUND GATA-1 AND ENHANCER-BOUND AP-1/NF-E2

被引:56
作者
GONG, QH [1 ]
DEAN, A [1 ]
机构
[1] NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892
关键词
D O I
10.1128/MCB.13.2.911
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We analyzed epsilon-globin transcription in erythroid cells and in erythroid extracts to determine the requirements for enhancer-dependent expression of this gene. Mutations that abolished GATA-1 binding at a single position in the promoter prevented interaction with enhancers, whereas elimination of a second more distal promoter GATA-1 site had no effect. Deletion or mutation of the GATA-1 sites in either the human beta-globin locus control region DNase-hypersensitive site II enhancer or the chicken beta(A)/epsilon-globin enhancer did not diminish the ability of the enhancers to interact with the promoter. In contrast, mutation of the AP-1/NF-E2 sites in these enhancers resulted in elimination of enhancement. In vitro transcription of these constructs was promoter dependent and was not sensitive to abolition of GATA-1 binding in the promoter, consistent with the role of GATA-1 solely as a mediator of the enhancer effect. Thus, GATA-1 regulates the response of the epsilon-globin gene to enhancers through a specific site in the promoter and requires enhancer AP-1/NF-E2 binding to transduce the enhancer effect on transcription.
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页码:911 / 917
页数:7
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