This study describes the construction and characterization of a "minilocus" containing the 5' and 3' flanking regions of the human β-globin gene, which was expressed in transgenic mice. The minilocus includes regulatory sequences that enable position-independent expression of the human β-globin gene, independent of its integration site in the genome. The expression level of the gene is directly related to its copy number and is comparable to that of the endogenous mouse β-globin gene. The results indicate that the DNA regions flanking the human β-globin locus contain dominant regulatory sequences that specify position-independent expression and normally activate the complete human multigene β-globin locus. The human β-globin gene is a cluster of five active genes, expressed in a tissue- and developmentally-specific manner. Mutations in this gene family lead to a range of genetic diseases, including β-thalassemia. The study identified several regulatory elements required for the appropriate expression of the human β-globin gene, including a positively acting globin-specific promoter element, a putatively negative regulatory promoter element, and two downstream regulatory sequences (enhancers). These elements are located immediately 5' and 3' of the β-globin gene. When the β-globin gene containing all these control regions is introduced into transgenic mice, the gene is not expressed at the same level as the mouse β-globin gene and exhibits position effects. This is characterized by variable expression of the transgene not correlated with the copy number of the injected gene. The study shows that the DNA sequences flanking the human β-globin gene contain dominant regulatory sequences that enable position-independent expression of the gene. These sequences are erythroid-specific and are present when any one of the globin genes is expressed. The study also shows that the human β-globin gene can be expressed at a level comparable to that of the mouse β-globin gene in transgenic mice. The results indicate that the DNA regions flanking the human β-globin locus contain dominant regulatory sequences that specify position-independent expression and normally activate the complete human multigene β-globin locus. The study concludes that the β-globin locus flanking sequences confer position-independent expression on the β-globin gene, which is expressed erythroid-specifically. The study also concludes that all of the regulatory sequences involved in β-globin gene expression are included in this construct.This study describes the construction and characterization of a "minilocus" containing the 5' and 3' flanking regions of the human β-globin gene, which was expressed in transgenic mice. The minilocus includes regulatory sequences that enable position-independent expression of the human β-globin gene, independent of its integration site in the genome. The expression level of the gene is directly related to its copy number and is comparable to that of the endogenous mouse β-globin gene. The results indicate that the DNA regions flanking the human β-globin locus contain dominant regulatory sequences that specify position-independent expression and normally activate the complete human multigene β-globin locus. The human β-globin gene is a cluster of five active genes, expressed in a tissue- and developmentally-specific manner. Mutations in this gene family lead to a range of genetic diseases, including β-thalassemia. The study identified several regulatory elements required for the appropriate expression of the human β-globin gene, including a positively acting globin-specific promoter element, a putatively negative regulatory promoter element, and two downstream regulatory sequences (enhancers). These elements are located immediately 5' and 3' of the β-globin gene. When the β-globin gene containing all these control regions is introduced into transgenic mice, the gene is not expressed at the same level as the mouse β-globin gene and exhibits position effects. This is characterized by variable expression of the transgene not correlated with the copy number of the injected gene. The study shows that the DNA sequences flanking the human β-globin gene contain dominant regulatory sequences that enable position-independent expression of the gene. These sequences are erythroid-specific and are present when any one of the globin genes is expressed. The study also shows that the human β-globin gene can be expressed at a level comparable to that of the mouse β-globin gene in transgenic mice. The results indicate that the DNA regions flanking the human β-globin locus contain dominant regulatory sequences that specify position-independent expression and normally activate the complete human multigene β-globin locus. The study concludes that the β-globin locus flanking sequences confer position-independent expression on the β-globin gene, which is expressed erythroid-specifically. The study also concludes that all of the regulatory sequences involved in β-globin gene expression are included in this construct.