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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-08-2579. This Article Full Text (PDF) All Versions of this Article: 2002-08-2579v1 101/11/4492    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 Yang, X. O Articles by Willerford, D. M Search for Related Content PubMed PubMed Citation Articles by Yang, X. O Articles by Willerford, D. M Social Bookmarking                   What's this? Submitted August 22, 2002 Accepted January 23, 2003 Regulation of T-cell receptor D1 promoter by KLF5 through reiterated GC-rich motifs Xuexian O Yang, Raymond T Doty, Justin S Hicks, and Dennis M Willerford* Departments of Medicine and Immunology, University of Washington, Seattle, WA, USA * Corresponding author; email: dwiller{at}u.washington.edu. Rearrangement of T-cell receptor (TCR) and immunoglobulin genes by a common V(D)J recombination machinery is regulated by developmentally specific chromatin changes at the target locus, a process associated with transcription. At the TCR locus, the E enhancer and the D1 promoter regulate germline transcription originating near the TCR D1 gene segment. The D1 promoter contains three GC-rich motifs that bound a common set of nuclear proteins from pro-T-cell lines. Mutations that diminished binding of nuclear proteins also diminished the activity of the D1 promoter in transcriptional reporter assays. Using a yeast one-hybrid approach, three Kruppel-like factors, KLF3, 5, and 6, and a novel zinc finger protein were identified in a thymus library, all of which bound the GC-rich motif in a sequence-specific manner. Of these genes, KLF5 mRNA was expressed in a restricted manner in lymphoid cells and tissues, with highest expression in pro-T cell lines and Rag-deficient thymocytes. Antibody supershift studies and chromatin immunoprecipitation assay confirmed that KLF5 bound the D1 promoter. In reporter gene assays, KLF5 but not KLF6 efficiently transactivated the D1 promoter, while a dominant-negative KLF5 construct inhibited reporter expression. These data suggest that reiterated GC-motifs contribute to germline TCR transcription through binding of KLF5 and other Kruppel family members, and that restricted expression of KLF5 may contribute to lineage-specific regulation of germline TCR transcription. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. Cao, A. K. Wara, B. Icli, X. Sun, R. R. S. Packard, F. Esen, C. J. Stapleton, M. Subramaniam, K. Kretschmer, I. Apostolou, et al. Kruppel-like Factor KLF10 Targets Transforming Growth Factor-{beta}1 to Regulate CD4+CD25- T Cells and T Regulatory Cells J. Biol. Chem., September 11, 2009; 284(37): 24914 - 24924. [Abstract] [Full Text] [PDF] N. Zhu, L. Gu, H. W. Findley, C. Chen, J.-T. Dong, L. Yang, and M. Zhou KLF5 Interacts with p53 in Regulating Survivin Expression in Acute Lymphoblastic Leukemia J. Biol. Chem., May 26, 2006; 281(21): 14711 - 14718. [Abstract] [Full Text] [PDF] M. C. van Zelm, M. van der Burg, D. de Ridder, B. H. Barendregt, E. F. E. de Haas, M. J. T. Reinders, A. C. Lankester, T. Revesz, F. J. T. Staal, and J. J. M. van Dongen Ig Gene Rearrangement Steps Are Initiated in Early Human Precursor B Cell Subsets and Correlate with Specific Transcription Factor Expression J. Immunol., November 1, 2005; 175(9): 5912 - 5922. [Abstract] [Full Text] [PDF] R. Rangel, M. R. McKeller, J. C. Sims-Mourtada, C. Kashi, K. Cain, E. D. Wieder, J. J. Molldrem, L. V. Pham, R. J. Ford, P. Yotnda, et al. Assembly of the {kappa} PreB Receptor Requires a V{kappa}-like Protein Encoded by a Germline Transcript J. Biol. Chem., May 6, 2005; 280(18): 17807 - 17814. [Abstract] [Full Text] [PDF]

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