The mammalian beta-globin locus is a multigenic, developmentally regulated, 
tissue-specific locus from which gene expression is regulated by a distal 
regulatory region, the locus control region (LCR). The functional mechanism by 
which the beta-globin LCR stimulates transcription of the linked beta-like 
globin genes remains unknown. The LCR is composed of a series of 5 DNaseI 
hypersensitive sites (5'HSs) that form in the nucleus of erythroid precursors. 
These HSs are conserved among mammals, bind transcription factors that also bind 
to other parts of the locus, and compose the functional components of the LCR. 
To test the hypothesis that individual HSs have unique properties, homologous 
recombination was used to construct 5 lines of mice with individual deletions of 
each of the 5'HSs of the endogenous murine beta-globin LCR. Here it is reported 
that deletion of 5'HS1 reduces expression of the linked genes by up to 24%, 
while deletion of 5'HS4 leads to reductions of up to 27%. These deletions do not 
perturb the normal stage-specific expression of genes from this multigenic 
locus. In conjunction with previous studies of deletions of the other HSs and 
studies of deletion of the entire LCR, it is concluded that (1) none of the 
5'HSs is essential for nearly normal expression; (2) none of the HSs is required 
for proper developmental expression; and (3) the HSs do not appear to synergize 
either structurally or functionally, but rather form independently and appear to 
contribute additively to the overall expression from the locus.