help button home button Endocrine Society Molecular Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on May 13, 2004
Molecular Endocrinology, doi:10.1210/me.2003-0351
A more recent version of this article appeared on August 1, 2004
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
18/8/1941    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow NURSA Molecule Pages Link
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Malo, M. S.
Right arrow Articles by Hodin, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Malo, M. S.
Right arrow Articles by Hodin, R. A.

Submitted on September 12, 2003
Accepted on May 3, 2004

Thyroid Hormone Positively Regulates the Enterocyte Differentiation Marker Intestinal Alkaline Phosphatase Gene via an Atypical Response Element

Madhu S. Malo, Wenying Zhang, Fuad Alkhoury, Premraj Pushpakaran, Mario A. Abedrapo, Moushumi Mozumder, Elizabeth Fleming, and Richard A. Hodin*

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

* To whom correspondence should be addressed. E-mail: rhodin{at}partners.org.

Thyroid hormone (T3) is a critical regulator of intestinal epithelial development and homeostasis, but its mechanism of action within the gut is not well understood. We have examined the molecular mechanisms underlying the T3 activation of the enterocyte differentiation marker intestinal alkaline phosphatase (IAP) gene. RT-PCR and western blotting showed that thyroid hormone receptors TR{alpha}1 and TR{beta}1 were expressed in human colorectal adenocarcinoma Caco-2 cells. Northern blotting detected expression of two IAP transcripts, which were increased approximately 3-fold in response to T3. Transient transfection studies with luciferase reporter plasmids carrying various internal and 5' deletion mutations of the IAP promoter localized a putative thyroid hormone response element (TRE) to a region approximately 620 nucleotides upstream (-620) of the ATG start codon. Electrophoretic mobility shift assays (EMSA) using TR{alpha}1-RXR{alpha} on sequential 5' and 3' single nucleotide deletions defined the TRE between -632 and -612 (5'-TTGAACTCAgccTGAGGTTAC-3'). Compared with the consensus TRE, the IAP-TRE is novel in that it contains an everted repeat of two nonamers (not hexamers) separated by 3 nucleotides. Neither TR{alpha}1 nor RXR{alpha} binds to the IAP-TRE; however, TR{beta}1 binds to this TRE with minimal affinity. In the presence of TR and RXR{alpha}, only the TR-RXR{alpha} heterodimer binds to the IAP-TRE. Mutagenesis of either nonamer abolishes the biological activity of IAP promoter. We have thus identified a novel response element that appears to mediate the T3-induced activation of the enterocyte differentiation marker, intestinal alkaline phosphatase.
Key words: Nuclear receptors • Thyroid hormone response element • Positive regulation • Enterocyte differentiation • Recombinant DNA

NURSA Molecule Pages Link:

Nuclear Receptors:   TRα  |  TRβ  |  RXRα
Ligands:   Thyroid hormone



This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
N. S. Belaguli, M. Zhang, M. Rigi, M. Aftab, and D. H. Berger
Cooperation between GATA4 and TGF-beta signaling regulates intestinal epithelial gene expression
Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1520 - G1533.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. Plateroti, E. Kress, J. I. Mori, and J. Samarut
Thyroid Hormone Receptor {alpha}1 Directly Controls Transcription of the {beta}-Catenin Gene in Intestinal Epithelial Cells
Mol. Cell. Biol., April 15, 2006; 26(8): 3204 - 3214.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. S. Malo, M. Mozumder, X. B. Zhang, S. Biswas, A. Chen, L.-C. Bai, J. L. Merchant, and R. A. Hodin
Intestinal alkaline phosphatase gene expression is activated by ZBP-89
Am J Physiol Gastrointest Liver Physiol, April 1, 2006; 290(4): G737 - G746.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
F. Alkhoury, M. S. Malo, M. Mozumder, G. Mostafa, and R. A. Hodin
Differential regulation of intestinal alkaline phosphatase gene expression by Cdx1 and Cdx2
Am J Physiol Gastrointest Liver Physiol, August 1, 2005; 289(2): G285 - G290.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2004 by The Endocrine Society