The histone methyltransferase Suv39h1 increases class switch recombination specifically to IgA
Bradley, Sean P. ; Kaminski, Denise A. ; Peters, Antoine H. F. M. ; Jenuwein, Thomas ; Stavnezer, Janet
Citations
Student Authors
Faculty Advisor
Academic Program
UMass Chan Affiliations
Document Type
Publication Date
Keywords
B-Cell-Specific Activator Protein
B-Lymphocytes
Binding Sites
Cells, Cultured
Histone-Lysine
N-Methyltransferase
Immunoglobulin A
*Immunoglobulin Class Switching
Methyltransferases
Mice
Mice, Inbred C57BL
Mice, Knockout
Plasmids
*Recombination, Genetic
Repressor Proteins
Life Sciences
Medicine and Health Sciences
Women's Studies
Subject Area
Embargo Expiration Date
Link to Full Text
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.
Source
J Immunol. 2006 Jul 15;177(2):1179-88.