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The Journal of Immunology, 2006, 177: 1179-1188.
Copyright © 2006 by The American Association of Immunologists

The Histone Methyltransferase Suv39h1 Increases Class Switch Recombination Specifically to IgA1

Sean P. Bradley2,*, Denise A. Kaminski*, Antoine H. F. M. Peters3,{dagger}, Thomas Jenuwein{dagger} and Janet Stavnezer4,*

* Immunology and Virology Program, Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655; and {dagger} Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria

Ab class (isotype) switching allows the humoral immune system to adaptively respond to different infectious organisms. Isotype switching occurs by intrachromosomal DNA recombination between switch (S) region sequences associated with CH region genes. Although isotype-specific transcription of unrearranged (germline) CH genes is required for switching, recent results suggest that isotype specificity is also determined by the sequences of downstream (acceptor) S regions. In the current study, we identify the histone methyltransferase Suv39h1 as a novel S{alpha}-specific factor that specifically increases IgA switching (Sµ-S{alpha} recombination) in a transiently transfected plasmid S substrate, and demonstrate that this effect requires the histone methyltransferase activity of Suv39h1. Additionally, B cells from Suv39h1-deficient mice have an isotype-specific reduction in IgA switching with no effect on the level of germline I{alpha}-C{alpha} transcripts. Taken together, our results suggest that Suv39h1 activity inhibits the activity of a sequence-specific DNA-binding protein that represses switch recombination to IgA.


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