Document Detail

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.
MedLine Citation:
PMID:  8537388     Owner:  NLM     Status:  MEDLINE    
We 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 approximately 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 extension 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 tha 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.
K G Danielson; J Pillarisetti; I R Cohen; B Sholehvar; K Huebner; L J Ng; J M Nicholls; K S Cheah; R V Iozzo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  270     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1995 Dec 
Date Detail:
Created Date:  1996-02-08     Completed Date:  1996-02-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  31225-34     Citation Subset:  IM    
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
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MeSH Terms
Base Sequence
Chromosome Mapping
Chromosomes, Human, Pair 3*
DNA, Complementary
Gene Expression Regulation, Developmental*
Hybrid Cells
Molecular Sequence Data
Poly A / metabolism
Promoter Regions, Genetic*
Proto-Oncogene Proteins / genetics*
RNA, Messenger / metabolism
Transcription, Genetic
Wnt Proteins
Grant Support
Reg. No./Substance:
0/DNA, Complementary; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/WNT5A protein, human; 0/Wnt Proteins; 24937-83-5/Poly A

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