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Essential function for SWI-SNF chromatin-remodeling complexes in the promoter-directed assembly of Tcrb genes

Nature Immunology volume 8, pages 809–816 (2007)Cite this article

Abstract

The assembly of genes encoding antigen receptors is regulated by developmental changes in chromatin that either permit or deny access to a single variable-(diversity)-joining recombinase. These changes are guided by transcriptional promoters and enhancers, which serve as accessibility-control elements in antigen-receptor loci. The function of each accessibility-control element and the factors they recruit to remodel chromatin remain obscure. Here we show that the recruitment of SWI-SNF chromatin-remodeling complexes compensated for the accessibility-control element function of a promoter but not an enhancer of the T cell receptor-β locus (Tcrb). Loss of SWI-SNF function in thymocytes inactivated recombinase targets at the endogenous Tcrb locus. Thus, initiation of Tcrb gene assembly and T cell development is contingent on the recruitment of SWI-SNF to promoters, which exposes gene segments to variable-(diversity)-joining recombinase.

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Figure 1: The association of BRG1 with DβJβ clusters is ACE-dependent.
Figure 2: ACE-dependent recruitment of BRG1 to a Tcrb mini-locus substrate.
Figure 3: Functional targeting of BRG1 to Tcrb mini-loci.
Figure 4: BRG1 restores ACE function in promoterless substrates.
Figure 5: Impaired Tcrb germline transcription after dominant inhibition of SWI-SNF function.
Figure 6: Depletion of BRG1 and BRM impairs transcription and rearrangement of DβJβ gene segments.

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Acknowledgements

We thank S. Smale (University of California at Los Angeles), J. Chen (Massachusetts Institute of Technology), M. Boothby (Vanderbilt University) and R. Kingston (Harvard University) for reagents, and F. Zhang for technical advice. Supported by the National Institutes of Health (P01 HL68744 and CA100905 to E.M.O.) and a Cancer Center Support Grant (P30 CA68485, Vanderbilt-Ingram Cancer Center).

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  1. Kenneth J Oestreich

    Present address: Present address: Rollins Research Center, Emory University, Atlanta, Georgia 30322, USA.,

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  1. Department of Microbiology and Immunology, Vanderbilt University, Nashville, 37232, Tennessee, USA

    Oleg Osipovich, Robin Milley Cobb, Kenneth J Oestreich, Steven Pierce & Eugene M Oltz

  2. Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale–Centre National de la Recherche Scientifique, Université de la Méditerranée, Marseille, Cedex, 09, France

    Pierre Ferrier

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Correspondence to Eugene M Oltz.

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Osipovich, O., Milley Cobb, R., Oestreich, K. et al. Essential function for SWI-SNF chromatin-remodeling complexes in the promoter-directed assembly of Tcrb genes. Nat Immunol 8, 809–816 (2007). https://doi.org/10.1038/ni1481

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