Abstract
The genomic architecture of protocadherin (Pcdh) gene clusters is remarkably similar to that of the immunoglobulin and T cell receptor gene clusters, and can potentially provide significant molecular diversity. Pcdh genes are abundantly expressed in the central nervous system. These molecules are primary candidates for establishing specific neuronal connectivity. Despite the extensive analyses of the genomic structure of both human and mouse Pcdh gene clusters, the definitive molecular mechanisms that control Pcdh gene expression are still unknown. Four theories have been proposed, including (1) DNA recombination followed by cis-splicing, (2) single promoter and cis-alternative splicing, (3) multiple promoters and cis-alternative splicing, and (4) multiple promoters and trans-splicing. Using a combination of molecular and genetic analyses, we evaluated the four models at the Pcdh-gamma locus. Our analysis provides evidence that the transcription of individual Pcdh-gamma genes is under the control of a distinct but related promoter upstream of each Pcdh-gamma variable exon, and posttranscriptional processing of each Pcdh-gamma transcript is predominantly mediated through cis-alternative splicing.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alleles
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Alternative Splicing / genetics*
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Animals
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COS Cells
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Cadherin Related Proteins
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Cadherins / biosynthesis
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Cadherins / genetics*
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Chlorocebus aethiops
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Embryo, Mammalian / cytology
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Exons / genetics
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Gene Expression Regulation*
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Gene Library
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Gene Rearrangement / genetics*
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Genes, Immunoglobulin
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Genes, Overlapping
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Models, Genetic
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Molecular Sequence Data
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics*
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Neurons / classification
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Neurons / metabolism*
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Promoter Regions, Genetic / genetics*
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Protein Isoforms / biosynthesis
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Protein Isoforms / genetics*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / genetics
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Recombination, Genetic
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Stem Cells / metabolism
Substances
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Cadherin Related Proteins
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Cadherins
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Gamma-protocadherins
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Nerve Tissue Proteins
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Protein Isoforms
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RNA, Messenger
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Recombinant Fusion Proteins
Associated data
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GENBANK/AF464151
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GENBANK/AF464152
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GENBANK/AF464153
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GENBANK/AF464154
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GENBANK/AF464155
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GENBANK/AF464159
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GENBANK/AF464163
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GENBANK/AF464164
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GENBANK/AF464165
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GENBANK/AF464166
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GENBANK/AF464167
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GENBANK/AF464168
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GENBANK/AF464169
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GENBANK/AF464170
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GENBANK/AF464171
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GENBANK/AF464172
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GENBANK/AF464173
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GENBANK/AF464174
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GENBANK/AF464175
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GENBANK/AF464176
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GENBANK/AF464177
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GENBANK/AF464178
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GENBANK/AF464179
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GENBANK/AF464180
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GENBANK/AF464181