The Expression Of Human βE-Globin Gene With Erythroid Enhancer In Transgenic Mice

The eight functional globin genes and three globin pseudogenes are arranged in two gene clusters: the αβ- and β- globin gene cluster. The α - globin gene cluster is located on the short arm of chromosome 16 and arranged in the order of 5' —ζ- ψζ- ψα1-α2-α1-θ-3' , spaning 30Kb; the β— globin gene cluster is on the short arm of chromosome 11 and in the order of 5' — ε-Gγ -Aγ-ψβ-δ-β- 3' , spaning over 60Kb. The DNA sequences of the two clusters have been determined.The expression of globin genes are characterized by 1) sequential expression of individual gene in each cluster, 2) erythroid — specific and developmental stage — specific expressions, and 3) balance between o.— like and β — like globin chains. The transcription of globin genes is regulated by the chromatin structure, methylation of globin genes and their flanking regions, local and distal cis —acting elements and cellular trans—acting factors.The β— globin gene locus control region (LCR) consists of four erythroid—specific DNase I hypersensitive sites (5'HS1 — 5' HS4) which are necessary for the high level expression of globin genes in erythroid tissues. The single 5' HS2, when linked to β- globin gene, can act as an erythroid enhancer in transfection and transgenic mice.Studies of expression regulation of eukaryotic genes in transgenic mice permit not only the devises of experiments on molecular level but also the observation of the involvement of almost all the factors affecting gene...