Title

The histone methyltransferase Suv39h1 increases class switch recombination specifically to IgA

UMMS Affiliation

Department of Molecular Genetics and Microbiology

Date

7-15-2006

Document Type

Article

Subjects

Animals; 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

Disciplines

Life Sciences | Medicine and Health Sciences | Women's Studies

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.

Rights and Permissions

Citation: J Immunol. 2006 Jul 15;177(2):1179-88.

Related Resources

Link to article in PubMed

PubMed ID

16818776