The beta-globin locus control region (LCR) is a large DNA element that is 
required for high-level expression of beta-like globin genes from the endogenous 
mouse locus or in transgenic mice carrying the human beta-globin locus. The LCR 
encompasses 6 DNaseI hypersensitive sites (HSs) that bind transcription factors. 
These HSs each contain a core of a few hundred base pairs (bp) that has most of 
the functional activity and exhibits high interspecies sequence homology. 
Adjoining the cores are 500- to 1000-bp "flanks" with weaker functional activity 
and lower interspecies homology. Studies of human beta-globin transgenes and of 
the endogenous murine locus show that deletion of an entire HS (core plus 
flanks) moderately suppresses expression. However, human transgenes in which 
only individual HS core regions were deleted showed drastic loss of expression 
accompanied by changes in chromatin structure. To address these disparate 
results, we have deleted the core region of 5'HS2 from the endogenous murine 
beta-LCR. The phenotype was similar to that of the larger 5'HS2 deletion, with 
no apparent disruption of chromatin structure. These results demonstrate that 
the greater severity of HS core deletions in comparison to full HS deletions is 
not a general property of the beta-LCR.