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Blood, Vol. 92 No. 11 (December 1), 1998:
pp. 4394-4403
Description and Targeted Deletion of 5 Hypersensitive Site 5 and 6 of the Mouse  -Globin Locus Control Region
M.A. Bender,
Andreas Reik,
Jennie Close,
Agnes Telling,
Elliot Epner,
Steven Fiering,
Ross Hardison, and
Mark Groudine
From the Fred Hutchinson Cancer Research Center, Seattle, WA; the
Departments of Pediatrics and Radiation Oncology, University of
Washington School of Medicine, Seattle, WA; the Department of
Microbiology, Dartmouth Medical School, Hanover, NH; and the Department
of Biochemistry and Molecular Biology, Pennsylvania State University,
University Park, PA.
The most upstream hypersensitive site (HS) of the
 -globin locus control region (LCR) in humans (5
HS 5) and chickens (5 HS 4) can act as an insulating element in
some gain of function assays and may demarcate a -globin domain. We
have mapped the most upstream HSs of the mouse -globin LCR and
sequenced this region. We find that mice have a region homologous to
human 5 HS 5 that is associated with a minor HS. In addition we
map a unique HS upstream of 5 HS 5 and refer to this novel site
as mouse 5 HS 6. We have also generated mice containing a
targeted deletion of the region containing 5 HS 5 and 6. We find
that after excision of the selectable marker in vivo, deletion of
5 HS 5 and 6 has a minimal effect on transcription and does not prevent formation of the remaining LCR HSs. Taken together these findings suggest that the most upstream HSs of the mouse -globin LCR
are not necessary for maintaining the -globin locus in an active
configuration or to protect it from a surrounding repressive chromatin
environment.
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