Published online before print
December 12, 2003
Genome Research, DOI: 10.1101/gr.1225204
Letter
Multiple Variable First Exons: A Mechanism for Cell- and Tissue-Specific Gene Regulation
Theresa Zhang1,3,
Peter Haws2,3 and
Qiang Wu2,4
1 Department of Bioinformatics, Merck Research Labs, Rahway, New Jersey 07065, USA
,
2 Department of Human Genetics, University of Utah Medical School, Salt Lake City, Utah 84112, USA
A large family of neural protocadherin (Pcdh) proteins is encoded by three closely linked mammalian gene clusters ( ,  , and  ). Pcdh and clusters have a striking genomic organization. Specifically, each "variable" exon is spliced to a common set of downstream "constant" exons within each cluster. Recent studies demonstrated that the cell-specific expression of each Pcdh gene is determined by a combination of variable-exon promoter activation and cis-splicing of the corresponding variable exon to the first constant exon. To determine whether there are other similarly organized gene clusters in mammalian genomes, we performed a genome-wide search and identified a large number of mammalian genes containing multiple variable first exons. Here we describe several clusters that contain about a dozen variable exons arrayed in tandem, including UDP glucuronosyltransferase (UGT1), plectin, neuronal nitric oxide synthase (NOS1), and glucocorticoid receptor (GR) genes. In all these cases, multiple variable first exons are each spliced to a common set of downstream constant exons to generate diverse functional mRNAs. As an example, we analyzed the tissue-specific expression profile of the mouse UGT1 repertoire and found that multiple isoforms are expressed in a tissue-specific manner. Therefore, this variable and constant genomic organization provides a genetic mechanism for directing distinct cell- and tissue-specific patterns of gene expression.
[Supplemental material is available online at www.genome.org. The sequence data described have been submitted to the GenBank/EMBL/DDDJ data library under accession nos. AY227194-AY227201, AY435128-AY435153 and AY480022-AY480051.]
Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.1225204. Article published online before print in December 2003.
3 These authors contributed equally to this work.
4 Corresponding author.
E-MAIL qwu{at}genetics.utah.edu; FAX (801) 585-7625.
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