Differential activation of intestinal gene promoters: functional interactions between GATA-5 and HNF-1 alpha.
The effects of GATA-4, -5, and -6, hepatocyte nuclear factor-1 alpha (HNF-1 alpha) and -beta, 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 alpha were strong activators of the LPH promoters, whereas HNF-1 alpha 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 alpha 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.
Krasinski
S D
SD
Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, The Floating Hospital for Children, New England Medical Center, and Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Van Wering
H M
HM
Tannemaat
M R
MR
Grand
R J
RJ
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D000071616:CDX2 Transcription Factor; D018938:Caco-2 Cells; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D050992:GATA5 Transcription Factor; D015971:Gene Expression Regulation, Enzymologic; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D010694:Lactase-Phlorizin Hydrolase / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000502:physiology*; D013394:Sucrase-Isomaltase Complex / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology; D014162:Transfection
D000071616:CDX2 Transcription Factor; D004268:DNA-Binding Proteins; D050992:GATA5 Transcription Factor; C494755:GATA5 protein, human; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D013394:Sucrase-Isomaltase Complex; D010694:Lactase-Phlorizin Hydrolase