J Biol Chem, Vol. 274, Issue 18, 12790-12796, April 30, 1999
A Composite Enhancer Element Directing Tissue-specific Expression
of Mouse Mammary Tumor Virus Requires both Ubiquitous and
Tissue-restricted Factors
Sandra L.
Grimm
and
Steven K.
Nordeen
¶
From the
Program in Molecular Biology and the
¶ Department of Pathology, University of Colorado Health Sciences
Center, Denver, Colorado 80262
Mouse mammary tumor virus (MMTV) expression is
restricted primarily to mammary epithelial cells. Sequences responsible
for both the mammary-specific expression of MMTV and the activation of
cellular oncogenes are located within two enhancer elements at the
5'-end of the long terminal repeat. Whereas the Ban2 enhancer (
1075
to
978) has been well characterized, the mammary-specific enhancer of
MMTV from
956 to
862 has only recently been recognized as a key
determinant of mammary-specific oncogene activation by MMTV. The
present study identifies and characterizes three binding sites located
within this element. Transient transfection of deletion and mutation
constructs shows that all three sites contribute to the basal
expression of MMTV in mammary cells. One of the binding activities
(footprint I) is restricted to mammary cells, whereas the other two
sites bind factors found in both mammary and nonmammary cells. The
multimerized mammary-specific enhancer of MMTV on its own can enhance a
minimal promoter in a mammary-specific fashion. However, the FpI
binding site alone cannot mediate this effect. Thus, it is the binding
of multiple factors in a combinatorial fashion that mediates the
mammary-restricted expression of MMTV.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.