Vol. 282, Issue 6, G1079-G1087, June 2002
Analysis of human cellular retinol-binding protein II
promoter during enterocyte differentiation
Liang
Zhang1,
Xueping
E1,
Kathryn
E.
Luker1,
Jian-Su
Shao1,
Marc S.
Levin1,3,
Eunran
Suh4, and
Ellen
Li1,2
Departments of 1 Medicine and
2 Biochemistry and Molecular Biophysics, Washington
University- St. Louis School of Medicine and
3 Specialty Care, St. Louis Veterans Administration
Medical Center, St. Louis, Missouri 63110; and
4 Department of Internal Medicine, University of
Pennsylvania School of Medicine, Philadelphia, Pennsylvania
19104
Cellular retinol binding protein II (CRBP
II) is a vitamin A-binding protein that is expressed specifically in
small intestinal villus absorptive cells. Previous studies have shown
that retinoic acid upregulates endogenous human CRBP II gene
expression in differentiated Caco-2 cells. To better characterize the
regulation of human CRBP II expression, we analyzed the ability of
receptor-selective agonists to enhance transcription from the
5'-upstream flanking region of the human CRBP II gene.
Stable transfection experiments showed that the proximal 2.8-kb region
of the human CRBP II gene is sufficient for retinoic acid
inducibility in differentiated Caco-2 cells. However, direct sequence
analysis and transient transfection experiments indicate that, unlike
the rat CRBP II promoter, the human CRBP II promoter is not a direct
retinoid X receptor target. The results indicate that the retinoic acid
responsiveness of the human CRBP II promoter is mediated by an indirect
mechanism and that this mechanism is associated with enterocyte differentiation.
gene regulation; retinoid X receptor; vitamin A; Caco-2
cells
