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Article: Characterization of the complete genomic structure of the human WNT-5A gene, functional analysis of its promoter, chromosomal mapping, and expression in early human embryogenesis

TitleCharacterization of the complete genomic structure of the human WNT-5A gene, functional analysis of its promoter, chromosomal mapping, and expression in early human embryogenesis
Authors
Issue Date1995
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 1995, v. 270 n. 52, p. 31225-31234 How to Cite?
AbstractWe report the complete genomic organization of the human WNT-5A gene, which encodes a cysteine-rich growth factor involved in cell-cell signaling during growth and differentiation. The gene comprises five exons with the terminal exon coding for a large 3'-untranslated region of ≃6.5 kilobase pairs and utilizes multiple polyadenylation signals to generate at least four discrete transcripts. We discovered a new leader exon interrupted by a 411- base pair intron that was retained in our original cDNA cloning. The promoter region was located in a GpC-rich island and harbored numerous cis-acting elements including several GC boxes and Sp1, AP1, and AP2 binding motifs. It lacked TATA or CAAT boxes typical of housekeeping and growth factor genes. In support of this, primer extension revealed two transcription start sites. Transient cell transfection assays showed functional promoter activity for the 3.9-kilobase pair 5'-flanking region. Interestingly, internal and 5' deletions revealed that the distal promoter was not required for full transcriptional activity and that the first 631 base pairs of WNT-5A harbored the strongest promoter activity. Using a panel of rodent-human hybrid DNAs carrying portions of chromosome 3p, we mapped the gene to 3p14.2-p21.1, between a constitutional and a familial renal cell carcinoma-associated translocation. In situ hybridization analyses of early human embryos at 28- 42 days of gestation revealed that WNT-5A transcripts were not restricted to the developing brain and limbs but were also observed in the mesenchyme bordering the pharyngeal clefts and pouches and in the developing gonads and kidneys. The relatively high expression in the celomic epithelium and in the precursors of follicles and seminiferous tubules suggest a novel role for WNT-5A in germ-cell differentiation. This study provides the molecular basis for discerning the regulation of the WNT-5A gene and offers the opportunity to investigate genetic disorders linked to this important gene.
Persistent Identifierhttp://hdl.handle.net/10722/48966
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDanielson, KGen_HK
dc.contributor.authorPillarisetti, Jen_HK
dc.contributor.authorCohen, IRen_HK
dc.contributor.authorSholehvar, Ben_HK
dc.contributor.authorHuebner, Ken_HK
dc.contributor.authorNg, LJen_HK
dc.contributor.authorNicholls, JMen_HK
dc.contributor.authorCheah, KSEen_HK
dc.contributor.authorIozzo, RVen_HK
dc.date.accessioned2008-06-12T06:30:57Z-
dc.date.available2008-06-12T06:30:57Z-
dc.date.issued1995en_HK
dc.identifier.citationJournal Of Biological Chemistry, 1995, v. 270 n. 52, p. 31225-31234en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/48966-
dc.description.abstractWe report the complete genomic organization of the human WNT-5A gene, which encodes a cysteine-rich growth factor involved in cell-cell signaling during growth and differentiation. The gene comprises five exons with the terminal exon coding for a large 3'-untranslated region of ≃6.5 kilobase pairs and utilizes multiple polyadenylation signals to generate at least four discrete transcripts. We discovered a new leader exon interrupted by a 411- base pair intron that was retained in our original cDNA cloning. The promoter region was located in a GpC-rich island and harbored numerous cis-acting elements including several GC boxes and Sp1, AP1, and AP2 binding motifs. It lacked TATA or CAAT boxes typical of housekeeping and growth factor genes. In support of this, primer extension revealed two transcription start sites. Transient cell transfection assays showed functional promoter activity for the 3.9-kilobase pair 5'-flanking region. Interestingly, internal and 5' deletions revealed that the distal promoter was not required for full transcriptional activity and that the first 631 base pairs of WNT-5A harbored the strongest promoter activity. Using a panel of rodent-human hybrid DNAs carrying portions of chromosome 3p, we mapped the gene to 3p14.2-p21.1, between a constitutional and a familial renal cell carcinoma-associated translocation. In situ hybridization analyses of early human embryos at 28- 42 days of gestation revealed that WNT-5A transcripts were not restricted to the developing brain and limbs but were also observed in the mesenchyme bordering the pharyngeal clefts and pouches and in the developing gonads and kidneys. The relatively high expression in the celomic epithelium and in the precursors of follicles and seminiferous tubules suggest a novel role for WNT-5A in germ-cell differentiation. This study provides the molecular basis for discerning the regulation of the WNT-5A gene and offers the opportunity to investigate genetic disorders linked to this important gene.en_HK
dc.format.extent418 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.subject.meshChromosomes, Human, Pair 3en_HK
dc.subject.meshGene Expression Regulation, Developmentalen_HK
dc.subject.meshPromoter Regions (Genetics)en_HK
dc.subject.meshProto-Oncogene Proteins - geneticsen_HK
dc.subject.meshBaRNA, Messenger - metabolismen_HK
dc.titleCharacterization of the complete genomic structure of the human WNT-5A gene, functional analysis of its promoter, chromosomal mapping, and expression in early human embryogenesisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=270&issue=52&spage=31225&epage=31234&date=1995&atitle=Characterization+of+the+complete+genomic+structure+of+the+human+WNT-5A+gene,+functional+analysis+of+its+promoter,+chromosomal+mapping,+and+expression+in+early+human+embryogenesisen_HK
dc.identifier.emailNicholls, JM:nicholls@pathology.hku.hken_HK
dc.identifier.emailCheah, KSE:hrmbdkc@hku.hken_HK
dc.identifier.authorityNicholls, JM=rp00364en_HK
dc.identifier.authorityCheah, KSE=rp00342en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1074/jbc.270.52.31225en_HK
dc.identifier.pmid8537388en_HK
dc.identifier.scopuseid_2-s2.0-0029617405en_HK
dc.identifier.hkuros20386-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0029617405&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume270en_HK
dc.identifier.issue52en_HK
dc.identifier.spage31225en_HK
dc.identifier.epage31234en_HK
dc.identifier.isiWOS:A1995TN44400056-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridDanielson, KG=7005379062en_HK
dc.identifier.scopusauthoridPillarisetti, J=6603504237en_HK
dc.identifier.scopusauthoridCohen, IR=7401817920en_HK
dc.identifier.scopusauthoridSholehvar, B=6505537565en_HK
dc.identifier.scopusauthoridHuebner, K=7101976858en_HK
dc.identifier.scopusauthoridNg, LJ=7201477760en_HK
dc.identifier.scopusauthoridNicholls, JM=7201463077en_HK
dc.identifier.scopusauthoridCheah, KSE=35387746200en_HK
dc.identifier.scopusauthoridIozzo, RV=35511430300en_HK

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