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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2003-12-10
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pubmed:abstractText |
We have examined the role that the transcription factor gut-enriched Krüppel-like factor (KLF4 or GKLF) plays in activating the enterocyte differentiation marker gene intestinal alkaline phosphatase (IAP). A yeast one-hybrid screen was used to identify proteins interacting with a previously identified cis-element (IF-III) located within the human IAP gene promoter. DNA-protein interactions were determined by using EMSA. Northern blot analysis was used to study RNA expression in human colon cancer RKO cells engineered to overexpress KLF4. Transient transfections with IAP-luciferase reporter constructs were used to characterize the mechanisms by which KLF4 activates IAP transcription. The yeast one-hybrid screen and EMSA identified KLF4 as binding to IF-III. RKO cells induced to overexpress KLF4 demonstrated a corresponding dose-dependent increase in IAP expression, and EMSA with nuclear extract from these cells confirmed that KLF4 binds to the IF-III element. Transient transfections revealed that KLF4 transactivated the IAP gene largely via a critical segment in the IAP promoter that includes the IF-III cis-element. Mutant KLF4 constructs failed to fully activate IAP. We have identified the enterocyte differentiation marker IAP as a KLF4 target gene. IAP transactivation by KLF4 is likely mediated through a critical region located within the proximal IAP promoter region.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0193-1857
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
286
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
G23-30
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12919939-Alkaline Phosphatase,
pubmed-meshheading:12919939-Animals,
pubmed-meshheading:12919939-Autoradiography,
pubmed-meshheading:12919939-Biological Markers,
pubmed-meshheading:12919939-Blotting, Northern,
pubmed-meshheading:12919939-COS Cells,
pubmed-meshheading:12919939-Cell Differentiation,
pubmed-meshheading:12919939-Cell Line,
pubmed-meshheading:12919939-Cercopithecus aethiops,
pubmed-meshheading:12919939-DNA-Binding Proteins,
pubmed-meshheading:12919939-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:12919939-Enterocytes,
pubmed-meshheading:12919939-Humans,
pubmed-meshheading:12919939-Intestines,
pubmed-meshheading:12919939-Kruppel-Like Transcription Factors,
pubmed-meshheading:12919939-Luciferases,
pubmed-meshheading:12919939-Promoter Regions, Genetic,
pubmed-meshheading:12919939-Recombinant Proteins,
pubmed-meshheading:12919939-Saccharomyces cerevisiae,
pubmed-meshheading:12919939-Transcription Factors,
pubmed-meshheading:12919939-Transcriptional Activation,
pubmed-meshheading:12919939-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor.
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pubmed:affiliation |
Deptartment of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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