Premium
The beta‐globin dominant control region: hypersensitive site 2.
Author(s) -
Philipsen S.,
Talbot D.,
Fraser P.,
Grosveld F.
Publication year - 1990
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1990.tb07385.x
Subject(s) - mill , biology , library science , history , archaeology , computer science
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.