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Cutting Edge: SWI/SNF Mediates Antisense Igh Transcription and Locus-Wide Accessibility in B Cell Precursors¹

Oleg A. Osipovich^2,*, Ramesh Subrahmanyam, Steven Pierce^*, Ranjan Sen and Eugene M. Oltz^2,3,*

^* Department of Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232; and Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224

The stepwise process of Ag receptor gene assembly, termed V(D)J recombination, is coordinated during lymphocyte development by sweeping changes in chromatin that permit or deny access to a single recombinase enzyme. We now show that switching/sucrose nonfermenting (SWI/SNF) chromatin remodeling complexes are recruited to the Igh locus by an enhancer-dependent process and that these complexes are essential for generating recombinase accessibility throughout the locus. Depletion of SWI/SNF in pro-B cells also inhibits antisense transcription through all clusters of Igh gene segments, a pioneering process that has been implicated in the initial opening of chromatin. We conclude that SWI/SNF complexes play multiple roles in Igh gene assembly, ranging from initial locus activation to the spreading and maintenance of chromatin accessibility over large V_H, D_H, and J_H domains.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work is supported by National Institutes of Health Grants AI 079732 and P30 CA68485 and by the Intramural Research Program of the National Institute of Aging (Baltimore, MD).

² Current address: Department of Pathology and Immunology, Washington University, St. Louis, MO 63110.

³ Address correspondence and reprint requests to Dr. Eugene Oltz, Department of Pathology and Immunology, Washington University School of Medicine, 660 Euclid Ave., Campus Box 8118, St. Louis, MO 63110. E-mail address: eoltz{at}pathology.wustl.edu

⁴ Abbreviations used in this paper: H3K9, histone 3 lysine 9; ST, antisense transcription; ChIP, chromatin immunoprecipitation; SWI/SNF, switching/sucrose nonfermenting.