The DNase I hypersensitive site 5' HS2 of the human beta-globin locus
control region confers position-independent, high-level expression on
the human beta-globin gene in transgenic mice. When a 5' HS2 beta-glob
in construct is flanked by retroviral vector sequences derived from Mo
loney Murine Leukemia Virus (MoMLV), expression of the beta-globin gen
e is severely inhibited. Apparently, one or more elements within the M
oMLV genome is capable of repressing transcription of the human beta-g
lobin gene in transgenic mice. A construct lacking the retroviral enha
ncer also fails to express the beta-globin gene, indicating that this
region of the virus is not essential for repression. Further analysis
may permit the identification of specific viral sequences that inhibit
gene expression; these sequences could then be deleted or mutated to
produce improved viral vectors.