title: The gamma-globin promoter has a major role in competitive inhibition of beta-globin gene expression in early erythroid development.
abstract: 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.
authors.affiliation: Department of Human Genetics, Medical College of Virginia of Virginia Commonwealth University, Richmond 23298-0033, USA.
authors.forename: T G
authors.initials: TG
authors.lastname: Sargent
authors.forename: A M
authors.initials: AM
authors.lastname: Buller
authors.forename: D T
authors.initials: DT
authors.lastname: Teachey
authors.forename: K S
authors.initials: KS
authors.lastname: McCanna
authors.forename: J A
authors.initials: JA
authors.lastname: Lloyd
mesh_terms: 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
chemical_list: D012313:RNA; D005914:Globins; D004247:DNA