The beta-globin dominant control region: hypersensitive site 2 - PubMed (original) (raw)

Comparative Study

The beta-globin dominant control region: hypersensitive site 2

S Philipsen et al. EMBO J. 1990 Jul.

Abstract

The Dominant Control Region (DCR) of the human beta-globin gene locus consists of four strong hypersensitive sites (HSS) upstream of the epsilon-globin gene. Addition of these sites confers copy number dependent expression on the human beta-globin gene in murine erythroleukaemia cells and transgenic mice, at levels comparable with the endogenous mouse globin genes. We have shown previously that a 1.9 kb fragment comprising HSS 2 accounts for 40-50% of the full effect of the DCR. In this paper we describe a deletional analysis of HSS 2. We show that a 225 bp fragment is sufficient to direct high levels of expression of the human beta-globin gene which is copy number dependent and integration site independent. This 225 bp fragment overlaps the major region that is hypersensitive 'in vivo'. DNase I footprinting shows the presence of four binding sites for the erythroid specific protein NF-E1; the three other footprinted regions display a remarkable redundancy of the sequence GGTGG and bind a number of proteins including Sp1 and the CACC box protein. The significance of these results for the regulation of globin gene expression is discussed.

PubMed Disclaimer

References

    1. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 - PubMed
    1. EMBO J. 1990 Jul;9(7):2169-77 - PubMed
    1. Prog Nucleic Acid Res Mol Biol. 1984;31:315-462 - PubMed
    1. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6384-8 - PubMed
    1. Science. 1985 Nov 1;230(4725):511-7 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources