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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-1-30
pubmed:abstractText
Assembly of tight junctions at the most apical part of the lateral cell membrane is a key event in the differentiation of polarized epithelial cells. Claudin-2, a transmembrane protein involved in tight junction strand formation, has turned out to play a crucial role for the paracellular barrier function by opening pores for small cations. Physiological and pathological variations of epithelial barrier function are accompanied by differential expression of tight junction proteins. Therefore, we characterized molecular mechanisms regulating claudin-2 gene expression. Genomic DNA containing the transcription start point of human claudin-2 was isolated and functionally characterized by reporter gene assays. Activity of the claudin-2 promoter was elevated in mouse mammary epithelial C57 cells expressing Wnt-1. LEF-1, a nuclear effector of the Wnt signaling pathway which is involved in the regulation of cell differentiation and polarization, was found to bind directly to the claudin-2 promoter as revealed by electrophoretic mobility shift assays. Expression of LEF-1 and beta-catenin both enhanced claudin-2 promoter activity. This increase was reduced after mutation of LEF-1 binding sites within the claudin-2 promoter. Furthermore, claudin-2 promoter activity was found to be enhanced by the TCF-4/beta-catenin transcription complex. Therefore, we conclude that gene expression mediated by the promoter of the human tight junction protein claudin-2 is regulated by factors involved in Wnt signaling. Moreover, a functional crosstalk between Wnt signaling and transcriptional activation related to caudal-related homeobox (Cdx) proteins could be demonstrated in the regulation of claudin-2 promoter-mediated gene expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
314
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1001-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14751232-Base Sequence, pubmed-meshheading:14751232-Cell Line, pubmed-meshheading:14751232-DNA, pubmed-meshheading:14751232-Electrophoretic Mobility Shift Assay, pubmed-meshheading:14751232-Gene Expression Regulation, pubmed-meshheading:14751232-Homeodomain Proteins, pubmed-meshheading:14751232-Humans, pubmed-meshheading:14751232-Membrane Proteins, pubmed-meshheading:14751232-Molecular Sequence Data, pubmed-meshheading:14751232-Mutagenesis, Site-Directed, pubmed-meshheading:14751232-Promoter Regions, Genetic, pubmed-meshheading:14751232-Proto-Oncogene Proteins, pubmed-meshheading:14751232-Signal Transduction, pubmed-meshheading:14751232-Transcriptional Activation, pubmed-meshheading:14751232-Wnt Proteins, pubmed-meshheading:14751232-Wnt1 Protein, pubmed-meshheading:14751232-Zebrafish Proteins
pubmed:year
2004
pubmed:articleTitle
Functional crosstalk between Wnt signaling and Cdx-related transcriptional activation in the regulation of the claudin-2 promoter activity.
pubmed:affiliation
Department of Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. joachim.mankertz@medizin.fu-berlin.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't