title: The histone methyltransferase Suv39h1 increases class switch recombination specifically to IgA.
abstract: 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 C(H) region genes. Although isotype-specific transcription of unrearranged (germline) C(H) 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 Salpha-specific factor that specifically increases IgA switching (Smu-Salpha 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 Ialpha-Calpha 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.
authors.affiliation: Immunology and Virology Program, Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Bradley
authors.forename: Denise A
authors.initials: DA
authors.lastname: Kaminski
authors.forename: Antoine H F M
authors.initials: AH
authors.lastname: Peters
authors.forename: Thomas
authors.initials: T
authors.lastname: Jenuwein
authors.forename: Janet
authors.initials: J
authors.lastname: Stavnezer
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites; D002478:Cells, Cultured; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007070:Immunoglobulin A / Q000235:genetics* / Q000378:metabolism; D017578:Immunoglobulin Class Switching; D008780:Methyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051757:PAX5 Transcription Factor / Q000378:metabolism; D010957:Plasmids; D011496:Protein Methyltransferases; D011995:Recombination, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D007070:Immunoglobulin A; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D012097:Repressor Proteins; C498700:Suv39h1 protein, mouse; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase