Clusterin gene transcription is activated by caudal-related homeobox genes in intestinal epithelium.
Caudal-related homeobox (Cdx) proteins play an important role in development and differentiation of the intestinal epithelium. Using cDNA differential display, we identified clusterin as a prominently induced gene in a Cdx2-regulated cellular model of intestinal differentiation. Transfection experiments and DNA-protein interaction assays showed that clusterin is an immediate downstream target gene for Cdx proteins. The distribution of clusterin protein in the intestine was assessed during development and in the adult epithelium using immunohistochemistry. In the adult mouse epithelium, clusterin protein was localized in both crypt and villus compartments but not in interstitial cells of the intestinal mucosa. Together, these data suggest that clusterin is a direct target gene for Cdx homeobox proteins, and the pattern of clusterin protein expression suggests that it is associated with the differentiated state in the intestinal epithelium.
Suh
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Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. suher@mail.med.upenn.edu
Wang
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Swain
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Tenniswood
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Traber
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D000367:Age Factors; D000818:Animals; D030161:Avian Proteins; D000071616:CDX2 Transcription Factor; D018938:Caco-2 Cells; D051152:Clusterin; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007422:Intestines / Q000166:cytology* / Q000502:physiology; D051379:Mice; D018832:Molecular Chaperones; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D016385:TATA Box / Q000502:physiology; D015534:Trans-Activators; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection
D030161:Avian Proteins; C491273:CDX1 protein, human; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C495242:CLU protein, human; C491272:Cdx1 protein, mouse; C491271:Cdx1 protein, rat; C495243:Clu protein, mouse; D051152:Clusterin; D006023:Glycoproteins; D018398:Homeodomain Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D015534:Trans-Activators