Article: Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3
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- Publisher Website: 10.1016/j.jpedsurg.2008.11.055
- Scopus: eid_2-s2.0-70350070157
- PMID: 19853745
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| Title | Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3 | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Leon, TYY1 Ngan, ESW1 Poon, HC1 So, MT1 Lui, VCH1 Tam, PKH1 GarciaBarcelo, MM1 | ||||||
| Keywords | Nkx2-1 Phox2b RET Transcription | ||||||
| Issue Date | 2009 | ||||||
| Publisher | WB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/jpedsurg | ||||||
| Citation | Journal Of Pediatric Surgery, 2009, v. 44 n. 10, p. 1904-1912 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.jpedsurg.2008.11.055 | ||||||
| Abstract | Background: The rearranged during transfection (RET) gene encodes a single-pass receptor whose proper expression and function are essential for the development of enteric nervous system. Mutations in RET regulatory regions are also associated with Hirschsprung disease (HSCR) (aganglionosis of the colon). We previously showed that 2 polymorphisms in RET promoter are associated with the increased risk of HSCR. These single nucleotide polymorphisms overlap with the NK2 homeobox 1 (Nkx2-1) binding motif interrupting the physical interaction of NKX2-1 with the RET promoter and result in reduced RET transcription. In this study, we further delineated Nkx2-1-mediated RET Transcription. Methods and results: First, we demonstrated that PHOX2B, like SOX10 and NKX2-1, is expressed in the mature enteric ganglions of human gut by immunohistochemistry. Second, subsequent dual-luciferase-reporter studies indicated that Nkx2-1 indeed works coordinately with Phox2b and Sox10, but not Pax3, to mediate RET transcription. In addition, identification of Phox2b responsive region in RET promoter further provides solid evidence of the potential functional interaction between Phox2b and RET. Conclusion: In sum, Phox2b and Sox10 act together with Nkx2.1 to modify RET signaling and this interaction may also contribute to HSCR susceptibility. © 2009 Elsevier Inc. All rights reserved. | ||||||
| ISSN | 0022-3468 2011 Impact Factor: 1.45 2011 SCImago Journal Rankings: 0.114 | ||||||
| DOI | http://dx.doi.org/10.1016/j.jpedsurg.2008.11.055 | ||||||
| ISI Accession Number ID | WOS:000271331700006
Funding Information: We extend our gratitude to everyone who participated in the study. This work was supported by research grants from the Hong Kong Research Grants Council (HKU 7654/07M) and the University of Hong Kong Seed Funding Programme for Basic Research (200611159028) to MMGB. | ||||||
| References | References in Scopus | ||||||
| Grants | Functional analysis of RET coding region mutations |
| dc.contributor.author | Leon, TYY | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Ngan, ESW | ||||||
| dc.contributor.author | Poon, HC | ||||||
| dc.contributor.author | So, MT | ||||||
| dc.contributor.author | Lui, VCH | ||||||
| dc.contributor.author | Tam, PKH | ||||||
| dc.contributor.author | GarciaBarcelo, MM | ||||||
| dc.date.accessioned | 2010-09-06T08:44:04Z | ||||||
| dc.date.available | 2010-09-06T08:44:04Z | ||||||
| dc.date.issued | 2009 | ||||||
| dc.description.abstract | Background: The rearranged during transfection (RET) gene encodes a single-pass receptor whose proper expression and function are essential for the development of enteric nervous system. Mutations in RET regulatory regions are also associated with Hirschsprung disease (HSCR) (aganglionosis of the colon). We previously showed that 2 polymorphisms in RET promoter are associated with the increased risk of HSCR. These single nucleotide polymorphisms overlap with the NK2 homeobox 1 (Nkx2-1) binding motif interrupting the physical interaction of NKX2-1 with the RET promoter and result in reduced RET transcription. In this study, we further delineated Nkx2-1-mediated RET Transcription. Methods and results: First, we demonstrated that PHOX2B, like SOX10 and NKX2-1, is expressed in the mature enteric ganglions of human gut by immunohistochemistry. Second, subsequent dual-luciferase-reporter studies indicated that Nkx2-1 indeed works coordinately with Phox2b and Sox10, but not Pax3, to mediate RET transcription. In addition, identification of Phox2b responsive region in RET promoter further provides solid evidence of the potential functional interaction between Phox2b and RET. Conclusion: In sum, Phox2b and Sox10 act together with Nkx2.1 to modify RET signaling and this interaction may also contribute to HSCR susceptibility. © 2009 Elsevier Inc. All rights reserved. | ||||||
| dc.description.grant | Functional analysis of RET coding region mutations | ||||||
| dc.description.grantcode | 96043 | ||||||
| dc.description.nature | postprint | ||||||
| dc.identifier.citation | Journal Of Pediatric Surgery, 2009, v. 44 n. 10, p. 1904-1912 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.jpedsurg.2008.11.055 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.jpedsurg.2008.11.055 | ||||||
| dc.identifier.epage | 1912 | ||||||
| dc.identifier.hkuros | 167940 | ||||||
| dc.identifier.isi | WOS:000271331700006
Funding Information: We extend our gratitude to everyone who participated in the study. This work was supported by research grants from the Hong Kong Research Grants Council (HKU 7654/07M) and the University of Hong Kong Seed Funding Programme for Basic Research (200611159028) to MMGB. | ||||||
| dc.identifier.issn | 0022-3468 2011 Impact Factor: 1.45 2011 SCImago Journal Rankings: 0.114 | ||||||
| dc.identifier.issue | 10 | ||||||
| dc.identifier.openurl | | ||||||
| dc.identifier.pmid | 19853745 | ||||||
| dc.identifier.scopus | eid_2-s2.0-70350070157 | ||||||
| dc.identifier.spage | 1904 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/83692 | ||||||
| dc.identifier.volume | 44 | ||||||
| dc.language | eng | ||||||
| dc.publisher | WB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/jpedsurg | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Journal of Pediatric Surgery | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||
| dc.subject.mesh | Enteric Nervous System - metabolism | ||||||
| dc.subject.mesh | Hirschsprung Disease - genetics | ||||||
| dc.subject.mesh | Homeodomain Proteins - genetics - metabolism | ||||||
| dc.subject.mesh | Proto-Oncogene Proteins c-ret - genetics - metabolism | ||||||
| dc.subject.mesh | Transcription Factors - genetics - metabolism | ||||||
| dc.subject | Nkx2-1 | ||||||
| dc.subject | Phox2b | ||||||
| dc.subject | RET | ||||||
| dc.subject | Transcription | ||||||
| dc.title | Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3 | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong