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Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3600-3604
Independent formation of DnaseI hypersensitive sites in the
murine  -globin locus control region
M. A. Bender,
Michelle G. Mehaffey,
Agnes Telling,
Bruce Hug,
Timothy J. Ley,
Mark Groudine, and
Steven Fiering
From the Fred Hutchinson Cancer Research Center, Seattle, WA;
Departments of Pediatrics and Radiation Oncology, University of
Washington, Seattle, WA; Departments of Internal Medicine and Genetics,
Washington University, St Louis, MO; and Department of Microbiology,
Dartmouth Medical School, Hanover, NH.
Mammalian  -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 -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
-globin regulation.
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