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1 Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, The Floating Hospital for Children, New England Medical Center, and 2 Tufts University School of Medicine and the Center for Gastroenterology Research on Absorptive and Secretory Processes, Boston 02111; 3 Tufts University School of Nutrition Science and Policy, Medford, Massachusetts 02155; 4 Free University of Amsterdam School of Medicine, 1081 HV Amsterdam; and 5 University of Amsterdam School of Medicine, 1105 AZ Amsterdam, The Netherlands
The effects of
GATA-4, -5, and -6, hepatocyte nuclear factor-1
(HNF-1) and -
,
and Cdx-2 on the rat and human lactase-phlorizin hydrolase (LPH) and
human sucrase-isomaltase (SI) promoters were studied using transient
cotransfection assays in Caco-2 cells. GATA factors and HNF-1 were
strong activators of the LPH promoters, whereas HNF-1 and Cdx-2 were
strong activators of the SI promoter, although GATA factors were also
necessary for maximal activation of the SI gene. Cotransfection of
GATA-5 and HNF-1 together resulted in a higher activation of all
three promoters than the sum of the activation by either factor alone,
demonstrating functional cooperativity. In the human LPH promoter, an
intact HNF-1 binding site was required for functional synergy. This
study is the first to demonstrate 1) differential activation
of the LPH and SI promoters by multiple transcription factors
cotransfected singly and in combination and 2) that GATA and
HNF-1 transcription factors cooperatively activate intestinal gene
promoters. Synergistic activation is a mechanism by which higher levels
of tissue-specific expression might be attained by overlapping
expression of specific transcription factors.
lactase-phlorizin hydrolase; sucrase-isomaltase; Cdx-2; hepatocyte nuclear factor-1
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