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Article: Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3
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TitleTranscriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3
 
AuthorsLeon, TYY1
Ngan, ESW1
Poon, HC1
So, MT1
Lui, VCH1
Tam, PKH1
GarciaBarcelo, MM1
 
KeywordsNkx2-1
Phox2b
RET
Transcription
 
Issue Date2009
 
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/jpedsurg
 
CitationJournal 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
 
AbstractBackground: 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.
 
ISSN0022-3468
2012 Impact Factor: 1.383
2012 SCImago Journal Rankings: 0.721
 
DOIhttp://dx.doi.org/10.1016/j.jpedsurg.2008.11.055
 
ISI Accession Number IDWOS:000271331700006
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 7654/07M
University of Hong Kong Seed Funding Programme200611159028
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLeon, TYY
 
dc.contributor.authorNgan, ESW
 
dc.contributor.authorPoon, HC
 
dc.contributor.authorSo, MT
 
dc.contributor.authorLui, VCH
 
dc.contributor.authorTam, PKH
 
dc.contributor.authorGarciaBarcelo, MM
 
dc.date.accessioned2010-09-06T08:44:04Z
 
dc.date.available2010-09-06T08:44:04Z
 
dc.date.issued2009
 
dc.description.abstractBackground: 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.naturepostprint
 
dc.identifier.citationJournal 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.doihttp://dx.doi.org/10.1016/j.jpedsurg.2008.11.055
 
dc.identifier.epage1912
 
dc.identifier.hkuros167940
 
dc.identifier.isiWOS:000271331700006
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 7654/07M
University of Hong Kong Seed Funding Programme200611159028
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.issn0022-3468
2012 Impact Factor: 1.383
2012 SCImago Journal Rankings: 0.721
 
dc.identifier.issue10
 
dc.identifier.openurl
 
dc.identifier.pmid19853745
 
dc.identifier.scopuseid_2-s2.0-70350070157
 
dc.identifier.spage1904
 
dc.identifier.urihttp://hdl.handle.net/10722/83692
 
dc.identifier.volume44
 
dc.languageeng
 
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/jpedsurg
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Pediatric Surgery
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshEnteric Nervous System - metabolism
 
dc.subject.meshHirschsprung Disease - genetics
 
dc.subject.meshHomeodomain Proteins - genetics - metabolism
 
dc.subject.meshProto-Oncogene Proteins c-ret - genetics - metabolism
 
dc.subject.meshTranscription Factors - genetics - metabolism
 
dc.subjectNkx2-1
 
dc.subjectPhox2b
 
dc.subjectRET
 
dc.subjectTranscription
 
dc.titleTranscriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong