The human beta-globin dominant control region (DCR) which flanks the multigene 
beta-globin locus directs high level, site of integration independent, copy 
number dependent expression on a linked human beta-globin gene in transgenic 
mice and stably transfected mouse erythroleukemia (MEL) cells. We have assayed 
each of the individual DNaseI hypersensitive regions present in the full 15kb 
DCR for position independence and copy number dependence of a linked beta-globin 
gene in transgenic mice. The results show that at least three of the individual 
DNaseI hypersensitive site regions (sites 1, 2 and 3), though expressing at 
lower levels than the full DCR, are capable of position independent, copy number 
dependent expression. Site 2 alone directs the highest level of expression of 
the single site constructs, producing nearly 70% of the level of the full DCR. 
Sites 1 and 3 each provide 30% of the full activity. Deletion of either site 2 
or 3 from the complete set significantly reduces the level of expression, but 
does not effect position independence or copy number dependence. This 
demonstrates that sites 2 and 3 are required for full expression and suggests 
that all the sites are required for the full expression of even a single gene 
from this multigene locus.