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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2557-2561. Prepublished online as a Blood First Edition Paper on November 17, 2005; DOI 10.1182/blood-2005-07-2957. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-07-2957v1 107/6/2557    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tan, J. S Articles by Conboy, J. G Search for Related Content PubMed PubMed Citation Articles by Tan, J. S Articles by Conboy, J. G Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 25, 2005 Accepted November 4, 2005 High frequency of alternative first exons in erythroid genes suggests a critical role in regulating gene function Jeff S Tan, Narla Mohandas, and John G Conboy* Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA Red Cell Physiology Laboratory, New York Blood Center, New York, NY, USA * Corresponding author; email: jgconboy{at}lbl.gov. The human genome employs alternative pre-mRNA splicing as an important mechanism to encode a complex proteome from a relatively small number of genes. An unknown number of these genes also possess multiple transcriptional promoters and alternative first exons that contribute another layer of complexity to gene expression mechanisms. Using a collection of over 100 erythroid-expressed genes as a test group, we utilized genome browser tools and genetic databases to assess the frequency of alternative first exons in the genome. Remarkably, 35% of these erythroid genes show evidence of alternative first exons. The majority of the candidate first exons are situated upstream of the coding exons, whereas a few are located internally within the gene. Computational analyses predict transcriptional promoters closely associated with many of the candidate first exons, supporting their authenticity. Importantly, the frequent presence of consensus translation initiation sites among the alternative first exons suggests that many proteins have alternative N-terminal structures whose expression can be coupled to promoter choice. These findings indicate that alternative promoters and first exons are more widespread in the human genome than previously appreciated and that they may play a major role in regulating expression of selected protein isoforms in a tissue-specific manner. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S.-C. Huang, A. Cho, S. Norton, E. S. Liu, J. Park, A. Zhou, I. D. Munagala, A. C. Ou, G. Yang, A. Wickrema, et al. Coupled transcription-splicing regulation of mutually exclusive splicing events at the 5' exons of protein 4.1R gene Blood, November 5, 2009; 114(19): 4233 - 4242. [Abstract] [Full Text] [PDF] J. W. Snow and S. H. Orkin Translational Isoforms of FOG1 Regulate GATA1-interacting Complexes J. Biol. Chem., October 23, 2009; 284(43): 29310 - 29319. [Abstract] [Full Text] [PDF] M. L. Yamamoto, T. A. Clark, S. L. Gee, J.-A. Kang, A. C. Schweitzer, A. Wickrema, and J. G. Conboy Alternative pre-mRNA splicing switches modulate gene expression in late erythropoiesis Blood, April 2, 2009; 113(14): 3363 - 3370. [Abstract] [Full Text] [PDF] A. P. W. Funnell, C. A. Maloney, L. J. Thompson, J. Keys, M. Tallack, A. C. Perkins, and M. Crossley Erythroid Kruppel-Like Factor Directly Activates the Basic Kruppel-Like Factor Gene in Erythroid Cells Mol. Cell. Biol., April 1, 2007; 27(7): 2777 - 2790. [Abstract] [Full Text] [PDF]

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