This Article Full Text Full Text (PDF) Supplemental Research Data All Versions of this Article: 1225204v1 14/1/79    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, T. Articles by Wu, Q. Search for Related Content PubMed PubMed Citation Articles by Zhang, T. Articles by Wu, Q. Social Bookmarking                   What's this?

Letter

Multiple Variable First Exons: A Mechanism for Cell- and Tissue-Specific Gene Regulation

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 familyof neural protocadherin (Pcdh) proteins is encoded bythree closelylinked 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 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 similarlyorganized 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.

³ These authors contributed equally to this work.

⁴ Corresponding author.
E-MAIL qwu{at}genetics.utah.edu; FAX (801) 585-7625.

[Supplemental material is available online at www.genome.org. The sequence data described have been submitted to the GenBank/EMBL/DDDJ data libraryunder accession nos. AY227194-AY227201, AY435128-AY435153 and AY480022-AY480051.]

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. X. L. Zhang, T. R. Searcy, Y. Wu, D. Gozal, and Y. Wang Alternative promoter usage and alternative splicing contribute to mRNA heterogeneity of mouse monocarboxylate transporter 2 Physiol Genomics, December 19, 2007; 32(1): 95 - 104. [Abstract] [Full Text] [PDF]

				R. S. Thomas, L. Pluta, L. Yang, and T. A. Halsey Application of Genomic Biomarkers to Predict Increased Lung Tumor Incidence in 2-Year Rodent Cancer Bioassays Toxicol. Sci., May 1, 2007; 97(1): 55 - 64. [Abstract] [Full Text] [PDF]

				M. L. Tress, P. L. Martelli, A. Frankish, G. A. Reeves, J. J. Wesselink, C. Yeats, P. l. Olason, M. Albrecht, H. Hegyi, A. Giorgetti, et al. The implications of alternative splicing in the ENCODE protein complement PNAS, March 27, 2007; 104(13): 5495 - 5500. [Abstract] [Full Text] [PDF]

				P. Moulin, Y. Guiot, J.-C. Jonas, J. Rahier, O. Devuyst, and J.-C. Henquin Identification and subcellular localization of the Na+/H+ exchanger and a novel related protein in the endocrine pancreas and adrenal medulla J. Mol. Endocrinol., March 1, 2007; 38(3): 409 - 422. [Abstract] [Full Text] [PDF]

				E. Kostova, C.H. Yeung, C.M. Luetjens, M. Brune, E. Nieschlag, and J. Gromoll Association of three isoforms of the meiotic BOULE gene with spermatogenic failure in infertile men Mol. Hum. Reprod., February 1, 2007; 13(2): 85 - 93. [Abstract] [Full Text] [PDF]

				D. Baek, C. Davis, B. Ewing, D. Gordon, and P. Green Characterization and predictive discovery of evolutionarily conserved mammalian alternative promoters Genome Res., February 1, 2007; 17(2): 145 - 155. [Abstract] [Full Text] [PDF]

				E. Presul, S. Schmidt, R. Kofler, and A. Helmberg Identification, tissue expression, and glucocorticoid responsiveness of alternative first exons of the human glucocorticoid receptor J. Mol. Endocrinol., January 1, 2007; 38(1): 79 - 90. [Abstract] [Full Text] [PDF]

				J. D. Lunemann, H. Gelderblom, M. Sospedra, J. A. Quandt, C. Pinilla, A. Marques, and R. Martin Cerebrospinal Fluid-Infiltrating CD4+ T Cells Recognize Borrelia burgdorferi Lysine-Enriched Protein Domains and Central Nervous System Autoantigens in Early Lyme Encephalitis Infect. Immun., January 1, 2007; 75(1): 243 - 251. [Abstract] [Full Text] [PDF]

				D. B. Buckley and C. D. Klaassen Tissue- and Gender-Specific mRNA Expression of UDP-Glucuronosyltransferases (UGTs) in Mice Drug Metab. Dispos., January 1, 2007; 35(1): 121 - 127. [Abstract] [Full Text] [PDF]

				P. Akiva, A. Toporik, S. Edelheit, Y. Peretz, A. Diber, R. Shemesh, A. Novik, and R. Sorek Transcription-mediated gene fusion in the human genome Genome Res., January 1, 2006; 16(1): 30 - 36. [Abstract] [Full Text] [PDF]

				T. Rhen and J. A. Cidlowski Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N. Engl. J. Med., October 20, 2005; 353(16): 1711 - 1723. [Full Text] [PDF]

				C.-M. Lin, H.-J. Chen, C. L. Leung, D. A. D. Parry, and R. K. H. Liem Microtubule actin crosslinking factor 1b: a novel plakin that localizes to the Golgi complex J. Cell Sci., August 15, 2005; 118(16): 3727 - 3738. [Abstract] [Full Text] [PDF]

				P. de la Grange, M. Dutertre, N. Martin, and D. Auboeuf FAST DB: a website resource for the study of the expression regulation of human gene products Nucleic Acids Res., July 28, 2005; 33(13): 4276 - 4284. [Abstract] [Full Text] [PDF]

				J. D. Choi, L. A. Underkoffler, A. J. Wood, J. N. Collins, P. T. Williams, J. A. Golden, E. F. Schuster Jr., K. M. Loomes, and R. J. Oakey A Novel Variant of Inpp5f Is Imprinted in Brain, and Its Expression Is Correlated with Differential Methylation of an Internal CpG Island Mol. Cell. Biol., July 1, 2005; 25(13): 5514 - 5522. [Abstract] [Full Text] [PDF]

				Q. Wu Comparative Genomics and Diversifying Selection of the Clustered Vertebrate Protocadherin Genes Genetics, April 1, 2005; 169(4): 2179 - 2188. [Abstract] [Full Text] [PDF]

				J. Harbig, R. Sprinkle, and S. A. Enkemann A sequence-based identification of the genes detected by probesets on the Affymetrix U133 plus 2.0 array Nucleic Acids Res., February 18, 2005; 33(3): e31 - e31. [Abstract] [Full Text] [PDF]

				S. Dike, V. S. Balija, L. U. Nascimento, Z. Xuan, J. Ou, T. Zutavern, L. E. Palmer, G. Hannon, M. Q. Zhang, and W. R. McCombie The mouse genome: Experimental examination of gene predictions and transcriptional start sites Genome Res., December 1, 2004; 14(12): 2424 - 2429. [Abstract] [Full Text] [PDF]