HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/G555    most recent 00011.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Wang, Z. Articles by Sibley, E. Search for Related Content PubMed PubMed Citation Articles by Wang, Z. Articles by Sibley, E.

MUCOSAL BIOLOGY

Transcriptional regulation of the lactase-phlorizin hydrolase promoter by PDX-1

Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305

Submitted 9 January 2004 ; accepted in final form 18 April 2004

Lactase-phlorizin hydrolase gene expression is spatially restricted along the anterior-posterior gut axis. Lactase gene transcription is maximal in the distal duodenum and jejunum in adult mammals and is barely detectable in the proximal duodenum. By contrast, pancreatic duodenal homeobox-1 (PDX-1) protein is expressed maximally in the proximal duodenum. This study aimed to determine the role of PDX-1 in regulating lactase gene promoter activity in intestinal epithelial cells. Caco-2 cells were cotransfected with lactase promoter-reporter constructs in the presence of a PDX-1 expression vector and assayed for luciferase activity. PDX-1 cotransfection results in repression of lactase promoter activity. Sequence analysis of the lactase promoter revealed a putative PDX-1 DNA binding site in the proximal 100-bp lactase gene promoter. EMSAs demonstrated that PDX-1 can interact with the lactase promoter binding site but not with a site in which the core PDX-1 binding sequence TAAT is mutated. Site-directed mutagenesis of the PDX-1 core binding site in the lactase promoter-reporter construct suggests that PDX-1 can function independently of DNA binding to its consensus binding site. Stable overexpression of PDX-1 results in repression of the endogenous human lactase gene in differentiated Caco-2 cells. Given the contrasting spatial expression pattern, PDX-1 may function to specify the anterior boundary of lactase expression in the small intestine and is thus a candidate regulator of anterior spatial restriction in the gut.

intestinal development; spatial restriction; repressor

This article has been cited by other articles:

				T. Bosse, H. M. van Wering, M. Gielen, L. N. Dowling, J. J. Fialkovich, C. M. Piaseckyj, F. J. Gonzalez, T. E. Akiyama, R. K. Montgomery, R. J. Grand, et al. Hepatocyte nuclear factor-1{alpha} is required for expression but dispensable for histone acetylation of the lactase-phlorizin hydrolase gene in vivo Am J Physiol Gastrointest Liver Physiol, May 1, 2006; 290(5): G1016 - G1024. [Abstract] [Full Text] [PDF]

				A. R. West and P. S. Oates Decreased sucrase and lactase activity in iron deficiency is accompanied by reduced gene expression and upregulation of the transcriptional repressor PDX-1 Am J Physiol Gastrointest Liver Physiol, December 1, 2005; 289(6): G1108 - G1114. [Abstract] [Full Text] [PDF]

				M. Brissova, M. Blaha, C. Spear, W. Nicholson, A. Radhika, M. Shiota, M. J. Charron, C. V. E. Wright, and A. C. Powers Reduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis Am J Physiol Endocrinol Metab, April 1, 2005; 288(4): E707 - E714. [Abstract] [Full Text] [PDF]