File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Transcriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3

TitleTranscriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3
Authors
KeywordsNkx2-1
Phox2b
RET
Transcription
Issue Date2009
PublisherWB 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?
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.
Persistent Identifierhttp://hdl.handle.net/10722/83692
ISSN
2014 Impact Factor: 1.387
2014 SCImago Journal Rankings: 0.724
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorLeon, TYYen_HK
dc.contributor.authorNgan, ESWen_HK
dc.contributor.authorPoon, HCen_HK
dc.contributor.authorSo, MTen_HK
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorTam, PKHen_HK
dc.contributor.authorGarciaBarcelo, MMen_HK
dc.date.accessioned2010-09-06T08:44:04Z-
dc.date.available2010-09-06T08:44:04Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Pediatric Surgery, 2009, v. 44 n. 10, p. 1904-1912en_HK
dc.identifier.issn0022-3468en_HK
dc.identifier.urihttp://hdl.handle.net/10722/83692-
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.en_HK
dc.languageengen_HK
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/jpedsurgen_HK
dc.relation.ispartofJournal of Pediatric Surgeryen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectNkx2-1en_HK
dc.subjectPhox2ben_HK
dc.subjectRETen_HK
dc.subjectTranscriptionen_HK
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.titleTranscriptional regulation of RET by Nkx2-1, Phox2b, Sox10, and Pax3en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-3468&volume=44&issue=10&spage=1904&epage=1912&date=2009&atitle=Transcriptional+regulation+of+RET+by+Nkx2-1,+Phox2b,+Sox10,+and+Pax3en_HK
dc.identifier.emailNgan, ESW: engan@hkucc.hku.hken_HK
dc.identifier.emailLui, VCH: vchlui@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hkucc.hku.hken_HK
dc.identifier.emailGarciaBarcelo, MM: mmgarcia@hkucc.hku.hken_HK
dc.identifier.authorityNgan, ESW=rp00422en_HK
dc.identifier.authorityLui, VCH=rp00363en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.identifier.authorityGarciaBarcelo, MM=rp00445en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1016/j.jpedsurg.2008.11.055en_HK
dc.identifier.pmid19853745en_HK
dc.identifier.scopuseid_2-s2.0-70350070157en_HK
dc.identifier.hkuros167940en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70350070157&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume44en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1904en_HK
dc.identifier.epage1912en_HK
dc.identifier.isiWOS:000271331700006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLeon, TYY=10641704600en_HK
dc.identifier.scopusauthoridNgan, ESW=22234827500en_HK
dc.identifier.scopusauthoridPoon, HC=35084222000en_HK
dc.identifier.scopusauthoridSo, MT=8748542200en_HK
dc.identifier.scopusauthoridLui, VCH=7004231344en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK
dc.identifier.scopusauthoridGarciaBarcelo, MM=6701767303en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats