The major regulatory element upstream of the alpha-globin gene has classical and inducible enhancer activity

Content Provider	Scilit
Author	Ren, S. Luo, Xn Atweh, Gf
Copyright Year	1993
Description	A major positive regulatory element has recently been identified 40 kb upstream from the human zeta 2-globin gene. This regulatory element increases the expression of a linked alpha-globin gene in mouse erythroleukemia cells and in transgenic mice. This element has been shown to share many of the structural and functional features of the locus control region (LCR) of the beta-globin gene cluster. We have examined the activity of a small fragment from this regulatory domain (alpha LCR) in a transient expression system. We show that this element is active as an enhancer in the erythroid environment of K562 cells. It is somewhat less effective as an enhancer in the nonerythroid environment of HeLa cells. This alpha LCR fragment does not exhibit promoter specificity because it can activate both the promoter of its endogenous target gene and the heterologous promoter of the SV40 early genes. Although the major activity of this element is mediated by its interaction with the promoter of the alpha-globin gene, some increase in activity is seen when structural elements from the 5′ end of the alpha-globin gene are included with the target promoter. In addition, we show that the enhancing activity of the alpha LCR is potentiated by hemin-induction of K562 cells. Whereas phorbol esters that induce megakaryocytic differentiation of K562 cells markedly decrease alpha- globin messenger RNA accumulation, they do not seem to have a negative effect on the activity of the alpha LCR. These studies suggest a role for the alpha LCR in the basal activity of the alpha-globin gene in erythroid cells and in its increased expression seen with erythroid differentiation. The mechanism of negative regulation of alpha-globin gene expression in phorbol-differentiated K562 cells does not appear to be mediated through the action of the alpha LCR.
Related Links	https://ashpublications.org/blood/article-pdf/81/4/1058/226427/1058.pdf
Ending Page	1066
Page Count	9
Starting Page	1058
DOI	10.1182/blood.v81.4.1058.bloodjournal8141058
Journal	Blood
Issue Number	4
Volume Number	81
Language	English
Publisher	American Society of Hematology
Publisher Date	1993-02-15
Access Restriction	Open
Subject Keyword	Biochemistry and Molecular Biology Differentiation Gene Expression Functional Alpha Globin Gene Activity A Major Increases the Expression Journal: Blood (Vol- 77, Issue- 4)
Content Type	Text
Resource Type	Article