Abstract
Antigen receptor genes undergo variable, diversity and joining (V(D)J) recombination, which requires ordered large-scale chromatin remodeling. Here we show that antisense transcription, both genic and intergenic, occurs extensively in the V region of the immunoglobulin heavy chain locus. RNA fluorescence in situ hybridization demonstrates antisense transcription is strictly developmentally regulated and is initiated during the transition from DJH to VDJH recombination and terminates concomitantly with VDJH recombination. Our data show antisense transcription is specific to the V region and suggest transcripts extend across several genes. We propose that antisense transcription remodels the V region to facilitate VH-to-DJH recombination. These findings have wider implications for V(D)J recombination of other antigen receptor loci and developmental regulation of multigene loci.
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Acknowledgements
We thank W. Reik, G. Butcher, J. Skok, J. Pell for critically reviewing this manuscript, and C. Osborne for technical help with RNA FISH. Supported by the Association for International Cancer Research (D.B.), Medical Research Council (A.E.C.) and Biotechnology and Biological Sciences Research Council (A.E.C. laboratory).
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Bolland, D., Wood, A., Johnston, C. et al. Antisense intergenic transcription in V(D)J recombination. Nat Immunol 5, 630–637 (2004). https://doi.org/10.1038/ni1068
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DOI: https://doi.org/10.1038/ni1068
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