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Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine
The caudal-related homeodomain transcription factors Cdx1 and Cdx2 are expressed in the developing endoderm with expression persisting into adulthood. Cdx1(−/−) mutants are viable and fertile and display no overt intestinal phenotype. Cdx2 null mutants are peri-implantation lethal; however, conditio...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559873/ https://www.ncbi.nlm.nih.gov/pubmed/23382958 http://dx.doi.org/10.1371/journal.pone.0054757 |
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author | Grainger, Stephanie Hryniuk, Alexa Lohnes, David |
author_facet | Grainger, Stephanie Hryniuk, Alexa Lohnes, David |
author_sort | Grainger, Stephanie |
collection | PubMed |
description | The caudal-related homeodomain transcription factors Cdx1 and Cdx2 are expressed in the developing endoderm with expression persisting into adulthood. Cdx1(−/−) mutants are viable and fertile and display no overt intestinal phenotype. Cdx2 null mutants are peri-implantation lethal; however, conditional mutation approaches have revealed that Cdx2 is required for patterning the intestinal epithelium and specification of the colon. Cdx2 is also necessary for homeostasis of the intestinal tract in the adult, where Cdx1 and Cdx2 appear to functionally overlap in the distal colon, but not during intestinal development. Cdx1 and Cdx2 exhibit complete overlap of expression in the intestine, although they differ in their relative levels, with Cdx1 maximal in the distal colon and Cdx2 peaking in the proximal cecum. Moreover, Cdx1 protein is graded along the crypt-villus axis, being abundant in the crypts and diminishing towards the villi. Cdx2 is expressed uniformly along this axis, but is differentially phosphorylated; the functional relevance of these expression domains and phosphorylation is currently unknown. Cdx1 and Cdx2 have been suggested to exhibit functional specificity in the intestinal tract. In the present study, using cell-based models, we found that relative to Cdx1, Cdx2 was significantly less potent at effecting a transcriptional response from the Cdx1 promoter, a known Cdx target gene. We subsequently assessed this relationship in vivo using a “gene swap” approach and found that Cdx2 cannot substitute for Cdx1 in this autoregulatory loop. This is in marked contrast with the ability of Cdx2 to support Cdx1 expression and function in paraxial mesoderm and vertebral patterning, thus providing novel in vivo evidence of context-dependent transcriptional specificity between these transcription factors. |
format | Online Article Text |
id | pubmed-3559873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35598732013-02-04 Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine Grainger, Stephanie Hryniuk, Alexa Lohnes, David PLoS One Research Article The caudal-related homeodomain transcription factors Cdx1 and Cdx2 are expressed in the developing endoderm with expression persisting into adulthood. Cdx1(−/−) mutants are viable and fertile and display no overt intestinal phenotype. Cdx2 null mutants are peri-implantation lethal; however, conditional mutation approaches have revealed that Cdx2 is required for patterning the intestinal epithelium and specification of the colon. Cdx2 is also necessary for homeostasis of the intestinal tract in the adult, where Cdx1 and Cdx2 appear to functionally overlap in the distal colon, but not during intestinal development. Cdx1 and Cdx2 exhibit complete overlap of expression in the intestine, although they differ in their relative levels, with Cdx1 maximal in the distal colon and Cdx2 peaking in the proximal cecum. Moreover, Cdx1 protein is graded along the crypt-villus axis, being abundant in the crypts and diminishing towards the villi. Cdx2 is expressed uniformly along this axis, but is differentially phosphorylated; the functional relevance of these expression domains and phosphorylation is currently unknown. Cdx1 and Cdx2 have been suggested to exhibit functional specificity in the intestinal tract. In the present study, using cell-based models, we found that relative to Cdx1, Cdx2 was significantly less potent at effecting a transcriptional response from the Cdx1 promoter, a known Cdx target gene. We subsequently assessed this relationship in vivo using a “gene swap” approach and found that Cdx2 cannot substitute for Cdx1 in this autoregulatory loop. This is in marked contrast with the ability of Cdx2 to support Cdx1 expression and function in paraxial mesoderm and vertebral patterning, thus providing novel in vivo evidence of context-dependent transcriptional specificity between these transcription factors. Public Library of Science 2013-01-30 /pmc/articles/PMC3559873/ /pubmed/23382958 http://dx.doi.org/10.1371/journal.pone.0054757 Text en © 2013 Grainger et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Grainger, Stephanie Hryniuk, Alexa Lohnes, David Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine |
title | Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine |
title_full | Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine |
title_fullStr | Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine |
title_full_unstemmed | Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine |
title_short | Cdx1 and Cdx2 Exhibit Transcriptional Specificity in the Intestine |
title_sort | cdx1 and cdx2 exhibit transcriptional specificity in the intestine |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559873/ https://www.ncbi.nlm.nih.gov/pubmed/23382958 http://dx.doi.org/10.1371/journal.pone.0054757 |
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