Mammalian beta-globin loci are composed of multiple orthologous genes whose 
expression is erythroid specific and developmentally regulated. The expression 
of these genes both from the endogenous locus and from transgenes is strongly 
influenced by a linked 15-kilobase region of clustered DNaseI hypersensitive 
sites (HSs) known as the locus control region (LCR). The LCR encompasses 5 major 
HSs, each of which is highly homologous among humans, mice, and other mammals. 
To analyze the function of individual HSs in the endogenous murine beta-globin 
LCR, we have used homologous recombination in embryonic stem cells to produce 5 
mouse lines, each of which is deficient for 1 of these major HSs. In this 
report, we demonstrate that deletion of the conserved region of 5'HS 1, 2, 3, 4, 
or 5/6 abolishes HS formation at the deletion site but has no influence on the 
formation of the remaining HSs in the LCR. Therefore, in the endogenous murine 
locus, there is no dominant or initiating site whose formation must precede the 
formation of the other HSs. This is consistent with the idea that HSs form 
autonomously. We discuss the implications of these findings for current models 
of beta-globin regulation.