Homeobox protein CDX-1

Homeobox protein CDX-1 is a protein in humans that is encoded by the CDX1 gene.^[5][6] CDX-1 is expressed in the developing endoderm and its expression persists in the intestine throughout adulthood.^[7] CDX-1 protein expression varies along the intestine, with high expression in intestinal crypts and diminishing expression along intestinal villi.^[8]

CDX1
Identifiers
Aliases	CDX1, caudal type homeobox 1, Homeobox protein CDX-1
External IDs	OMIM: 600746; MGI: 88360; HomoloGene: 1366; GeneCards: CDX1; OMA:CDX1 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q32 Start 150,166,778 bp[1] End 150,184,558 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 E1|18 34.41 cM Start 61,151,934 bp[2] End 61,169,271 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of transverse colon rectum mucosa of ileum mucosa of sigmoid colon duodenum gonad jejunal mucosa testicle epithelium of colon appendix Top expressed in left colon crypt of lieberkuhn of small intestine ileum primitive streak Ileal epithelium duodenum Paneth cell jejunum embryo migratory enteric neural crest cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA-binding transcription factor activity RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA binding sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific protein binding DNA-binding transcription factor activity, RNA polymerase II-specific methyl-CpG binding RNA polymerase II transcription regulatory region sequence-specific DNA binding Cellular component nucleus Biological process animal organ morphogenesis multicellular organism development pattern specification process bone morphogenesis cell differentiation anterior/posterior axis specification regulation of transcription, DNA-templated regulation of somitogenesis positive regulation of transcription by RNA polymerase II anterior/posterior pattern specification transcription by RNA polymerase II transcription, DNA-templated regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1044 12590 Ensembl ENSG00000113722 ENSMUSG00000024619 UniProt P47902 P18111 RefSeq (mRNA) NM_001804 NM_009880 RefSeq (protein) NP_001795 NP_034010 Location (UCSC) Chr 5: 150.17 – 150.18 Mb Chr 18: 61.15 – 61.17 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene is a member of the caudal-related homeobox transcription factor family. The encoded DNA-binding protein regulates intestine-specific gene expression and enterocyte differentiation. It has been shown to induce expression of the intestinal alkaline phosphatase gene, and inhibit beta-catenin/T-cell factor transcriptional activity.^[6]

CDX1 has also been shown to play an important role in embryonic epicardial development. It has been demonstrated that CDX proteins suppress cardiac differentiation in both zebrafish and mouse embryonic stem cells, but the overall mechanism for how this happens is poorly understood.^[9] However, CDX1 has been shown to be transiently expressed in the embryonic heart 11.5 days post coitum (dpc). This transient expression is thought to induce epicardial epithelial-to-mesenchymal transition and thus proper cardiovascular formation. It has been shown that low-dose CDX1 induction caused enhanced migration and differentiation of epicardium-derived cells into vascular smooth muscle, where as continued high dose induction of CDX1 or CDX1 deficiency diminished the ability of these cells to migrate and differentiate into smooth muscle by the actions of TGF-β1. Furthermore, CDX1 induction also altered transcript expression of genes related to cell adhesions for EMT and angiogenesis.^[10] Therefore, along with its known roles in intestinal patterning and differentiation, CDX1 is also shown to be important in epicardial development.

References

1. GRCh38: Ensembl release 89: ENSG00000113722 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024619 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Bonner CA, Loftus SK, Wasmuth JJ (July 1995). "Isolation, characterization, and precise physical localization of human CDX1, a caudal-type homeobox gene". Genomics. 28 (2): 206–211. doi:10.1006/geno.1995.1132. PMID 8530027.
6. "Entrez Gene: CDX1 caudal type homeobox transcription factor 1".
7. Grainger S, Hryniuk A, Lohnes D (2013). "Cdx1 and Cdx2 exhibit transcriptional specificity in the intestine". PLOS ONE. 8 (1): e54757. Bibcode:2013PLoSO...854757G. doi:10.1371/journal.pone.0054757. PMC 3559873. PMID 23382958.
8. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. (October 2007). "Identification of stem cells in small intestine and colon by marker gene Lgr5". Nature. 449 (7165): 1003–1007. Bibcode:2007Natur.449.1003B. doi:10.1038/nature06196. PMID 17934449. S2CID 4349637.
9. Lengerke C, Wingert R, Beeretz M, Grauer M, Schmidt AG, Konantz M, et al. (June 2011). "Interactions between Cdx genes and retinoic acid modulate early cardiogenesis". Developmental Biology. 354 (1): 134–142. doi:10.1016/j.ydbio.2011.03.027. PMC 3502019. PMID 21466798.
10. Chu M, Wang L, Wang H, Shen T, Yang Y, Sun Y, et al. (2014). "A novel role of CDX1 in embryonic epicardial development". PLOS ONE. 9 (7): e103271. Bibcode:2014PLoSO...9j3271C. doi:10.1371/journal.pone.0103271. PMC 4113346. PMID 25068460.

Further reading

• "Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome. The Treacher Collins Syndrome Collaborative Group". Nature Genetics. 12 (2): 130–136. February 1996. doi:10.1038/ng0296-130. PMID 8563749. S2CID 34312227.
• Mallo GV, Rechreche H, Frigerio JM, Rocha D, Zweibaum A, Lacasa M, et al. (February 1997). "Molecular cloning, sequencing and expression of the mRNA encoding human Cdx1 and Cdx2 homeobox. Down-regulation of Cdx1 and Cdx2 mRNA expression during colorectal carcinogenesis". International Journal of Cancer. 74 (1): 35–44. doi:10.1002/(SICI)1097-0215(19970220)74:1<35::AID-IJC7>3.0.CO;2-1. PMID 9036867.
• Mizoshita T, Inada K, Tsukamoto T, Kodera Y, Yamamura Y, Hirai T, et al. (2002). "Expression of Cdx1 and Cdx2 mRNAs and relevance of this expression to differentiation in human gastrointestinal mucosa--with special emphasis on participation in intestinal metaplasia of the human stomach". Gastric Cancer. 4 (4): 185–191. doi:10.1007/PL00011741. PMID 11846061.
• Suh ER, Ha CS, Rankin EB, Toyota M, Traber PG (September 2002). "DNA methylation down-regulates CDX1 gene expression in colorectal cancer cell lines". The Journal of Biological Chemistry. 277 (39): 35795–35800. doi:10.1074/jbc.M205567200. PMID 12124393.
• Domon-Dell C, Schneider A, Moucadel V, Guerin E, Guenot D, Aguillon S, et al. (September 2003). "Cdx1 homeobox gene during human colon cancer progression". Oncogene. 22 (39): 7913–7921. doi:10.1038/sj.onc.1206756. PMID 12970739.
• Wong NA, Britton MP, Choi GS, Stanton TK, Bicknell DC, Wilding JL, et al. (January 2004). "Loss of CDX1 expression in colorectal carcinoma: promoter methylation, mutation, and loss of heterozygosity analyses of 37 cell lines". Proceedings of the National Academy of Sciences of the United States of America. 101 (2): 574–579. Bibcode:2004PNAS..101..574W. doi:10.1073/pnas.0307190101. PMC 327189. PMID 14704280.
• Rankin EB, Xu W, Silberg DG, Suh E (May 2004). "Putative intestine-specific enhancers located in 5' sequence of the CDX1 gene regulate CDX1 expression in the intestine" (PDF). American Journal of Physiology. Gastrointestinal and Liver Physiology. 286 (5): G872–G880. doi:10.1152/ajpgi.00326.2003. PMID 14715525. S2CID 18376885. Archived from the original (PDF) on 2019-03-07.
• Béland M, Pilon N, Houle M, Oh K, Sylvestre JR, Prinos P, et al. (June 2004). "Cdx1 autoregulation is governed by a novel Cdx1-LEF1 transcription complex". Molecular and Cellular Biology. 24 (11): 5028–5038. doi:10.1128/MCB.24.11.5028-5038.2004. PMC 416402. PMID 15143193.
• Guo RJ, Huang E, Ezaki T, Patel N, Sinclair K, Wu J, et al. (August 2004). "Cdx1 inhibits human colon cancer cell proliferation by reducing beta-catenin/T-cell factor transcriptional activity". The Journal of Biological Chemistry. 279 (35): 36865–36875. doi:10.1074/jbc.M405213200. PMID 15215241.
• Alkhoury F, Malo MS, Mozumder M, Mostafa G, Hodin RA (August 2005). "Differential regulation of intestinal alkaline phosphatase gene expression by Cdx1 and Cdx2" (PDF). American Journal of Physiology. Gastrointestinal and Liver Physiology. 289 (2): G285–G290. doi:10.1152/ajpgi.00037.2005. PMID 15774940. S2CID 1066204. Archived from the original (PDF) on 2019-03-02.
• Wong NA, Wilding J, Bartlett S, Liu Y, Warren BF, Piris J, et al. (May 2005). "CDX1 is an important molecular mediator of Barrett's metaplasia". Proceedings of the National Academy of Sciences of the United States of America. 102 (21): 7565–7570. Bibcode:2005PNAS..102.7565W. doi:10.1073/pnas.0502031102. PMC 1140438. PMID 15894614.

External links

• Human CDX1 genome location and CDX1 gene details page in the UCSC Genome Browser.
• CDX1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.