Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation
Copyright policy )Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation
Activation-induced cytidine deaminase (AID) is shown to be essential and sufficient to induce two genetic alterations in the Ig loci: class switch recombination (CSR) and somatic hypermutation (SHM). However, it is still unknown how a single-molecule AID differentially regulates CSR and SHM. Here we identified Spt6 as an AID-interacting protein by yeast two-hybrid screening and immunoprecipitation followed by mass spectrometry. Knockdown of Spt6 resulted in severe reduction of CSR in both the endogenous Ig locus in B cells and an artificial substrate in fibroblast cells. Conversely, knockdown of Spt6 did not reduce but slightly enhanced SHM in an artificial substrate in B cells, indicating that Spt6 is required for AID to induce CSR but not SHM. These results suggest that Spt6 is involved in differential regulation of CSR and SHM by AID.
B-Lymphocytes, AICDA (Activation-Induced Cytidine Deaminase), Base Sequence, 500, Immunoglobulin Class Switching, Recombinant Proteins, Cell Line, Histones, Mice, Cytidine Deaminase, Gene Knockdown Techniques, Two-Hybrid System Techniques, Animals, Humans, Mutant Proteins, Protein Interaction Domains and Motifs, Somatic Hypermutation, Immunoglobulin, DNA Primers, Molecular Chaperones, Sequence Deletion, Transcription Factors
B-Lymphocytes, AICDA (Activation-Induced Cytidine Deaminase), Base Sequence, 500, Immunoglobulin Class Switching, Recombinant Proteins, Cell Line, Histones, Mice, Cytidine Deaminase, Gene Knockdown Techniques, Two-Hybrid System Techniques, Animals, Humans, Mutant Proteins, Protein Interaction Domains and Motifs, Somatic Hypermutation, Immunoglobulin, DNA Primers, Molecular Chaperones, Sequence Deletion, Transcription Factors
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