RGD Reference Report - Multiple variable first exons: a mechanism for cell- and tissue-specific gene regulation. - Rat Genome Database

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Multiple variable first exons: a mechanism for cell- and tissue-specific gene regulation.

Authors: Zhang, T  Haws, P  Wu, Q 
Citation: Zhang T, etal., Genome Res 2004 Jan;14(1):79-89. Epub 2003 Dec 12.
RGD ID: 1302827
Pubmed: PMID:14672974   (View Abstract at PubMed)
PMCID: PMC314283   (View Article at PubMed Central)
DOI: DOI:10.1101/gr.1225204   (Journal Full-text)

A large family of neural protocadherin (Pcdh) proteins is encoded by three closely linked mammalian gene clusters (alpha, beta, and gamma). Pcdh alpha and gamma 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 bya 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.

Objects referenced in this article
Gene Ugt1a1 UDP glucuronosyltransferase 1 family, polypeptide A1 Mus musculus
Gene Ugt1a2 UDP glucuronosyltransferase 1 family, polypeptide A2 Mus musculus
Gene Ugt1a6a UDP glucuronosyltransferase 1 family, polypeptide A6A Mus musculus
Gene Gcnt2 glucosaminyl (N-acetyl) transferase 2 Rattus norvegicus
Gene Gcnt3 glucosaminyl (N-acetyl) transferase 3, mucin type Rattus norvegicus
Gene Nos1 nitric oxide synthase 1 Rattus norvegicus
Gene Nr3c1 nuclear receptor subfamily 3, group C, member 1 Rattus norvegicus
Gene Pcdha12 protocadherin alpha 12 Rattus norvegicus
Gene Pcdhb1 protocadherin beta 1 Rattus norvegicus
Gene Pcdhb10 protocadherin beta 10 Rattus norvegicus
Gene Pcdhb11 protocadherin beta 11 Rattus norvegicus
Gene Pcdhb14 protocadherin beta 14 Rattus norvegicus
Gene Pcdhb15 protocadherin beta 15 Rattus norvegicus
Gene Pcdhb17 protocadherin beta 17 Rattus norvegicus
Gene Pcdhb18 protocadherin beta 18 Rattus norvegicus
Gene Pcdhb19 protocadherin beta 19 Rattus norvegicus
Gene Pcdhb21 protocadherin beta 21 Rattus norvegicus
Gene Pcdhb22 protocadherin beta 22 Rattus norvegicus
Gene Pcdhb3 protocadherin beta 3 Rattus norvegicus
Gene Pcdhb4 protocadherin beta 4 Rattus norvegicus
Gene Pcdhb5 protocadherin beta 5 Rattus norvegicus
Gene Pcdhb6 protocadherin beta 6 Rattus norvegicus
Gene Pcdhb7 protocadherin beta 7 Rattus norvegicus
Gene Pcdhb8 protocadherin beta 8 Rattus norvegicus
Gene Plec plectin Rattus norvegicus
Gene Ugt1a1 UDP glucuronosyltransferase family 1 member A1 Rattus norvegicus
Gene Ugt1a2 UDP glucuronosyltransferase 1 family, polypeptide A2 Rattus norvegicus
Gene Ugt1a3 UDP glycosyltransferase 1 family, polypeptide A3 Rattus norvegicus
Gene Ugt1a6 UDP glucuronosyltransferase family 1 member A6 Rattus norvegicus
Gene Ugt1a7c UDP glucuronosyltransferase 1 family, polypeptide A7C Rattus norvegicus
Gene Ugt1a8 UDP glucuronosyltransferase family 1 member A8 Rattus norvegicus
Gene Ugt1a9 UDP glucuronosyltransferase family 1 member A9 Rattus norvegicus

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