The gamma-globin promoter has a major role in competitive inhibition of beta-globin gene expression in early erythroid development.
The human gamma-globin gene competitively inhibits beta-globin gene expression in early erythroid development. To identify the gamma-globin gene sequences required for this effect, transgenic mice and stable transfection analyses with constructs containing 5'HS2 from the locus control region, modified gamma-globin genes, and the beta-globin gene were used. The -136 to +56 region of the gamma-globin promoter is necessary for competitive inhibition, as the beta-globin gene was inappropriately expressed in mouse embryos and in K562 and HEL cells containing constructs in which this region was deleted. Independently, the -140 to +56 region of gamma-globin gene was not sufficient to inhibit beta-globin transcription in mouse embryos or in cultured cells. Competitive inhibition of beta-globin gene expression was observed in K562 and HEL cells having a gamma-globin gene with a -161 promoter. The data suggest that the -161 gamma-globin promoter, which includes the CACCC box, two CCAAT boxes, the stage selector element (SSE), and TATA box, has a major role in suppressing beta-globin transcription early in development. Proteins binding to these or other gamma-globin promoter elements may interact with those binding to the locus control region, consequently precluding beta-globin transcription.
Sargent
T G
TG
Department of Human Genetics, Medical College of Virginia of Virginia Commonwealth University, Richmond 23298-0033, USA.
Buller
A M
AM
Teachey
D T
DT
McCanna
K S
KS
Lloyd
J A
JA
D000818:Animals; D004247:DNA / Q000032:analysis; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012313:RNA / Q000032:analysis
D012313:RNA; D005914:Globins; D004247:DNA