Wang Xiaozhong, Su Hong, Bradley Allan
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Genes Dev. 2002 Aug 1;16(15):1890-905. doi: 10.1101/gad.1004802.
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.
原钙黏蛋白（Pcdh）基因簇的基因组结构与免疫球蛋白和T细胞受体基因簇的基因组结构非常相似，并且可能提供显著的分子多样性。Pcdh基因在中枢神经系统中大量表达。这些分子是建立特定神经元连接的主要候选分子。尽管对人类和小鼠Pcdh基因簇的基因组结构进行了广泛分析，但控制Pcdh基因表达的明确分子机制仍然未知。已经提出了四种理论，包括（1）DNA重组后进行顺式剪接，（2）单一启动子和顺式可变剪接，（3）多个启动子和顺式可变剪接，以及（4）多个启动子和反式剪接。我们结合分子和遗传分析，在Pcdh-γ基因座评估了这四种模型。我们的分析提供了证据，表明各个Pcdh-γ基因的转录受每个Pcdh-γ可变外显子上游一个独特但相关的启动子控制，并且每个Pcdh-γ转录本的转录后加工主要通过顺式可变剪接介导。
