title: Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation.
abstract: 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.
authors.affiliation: Department of Immunology and Genomic Medicine, Frontier Technology Center, Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Il-mi
authors.initials: IM
authors.lastname: Okazaki
authors.forename: Katsuya
authors.initials: K
authors.lastname: Okawa
authors.forename: Maki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kiyotsugu
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Shimpei
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagaoka
authors.forename: Reiko
authors.initials: R
authors.lastname: Shinkura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kitawaki
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.forename: Shun-Ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism; D006801:Humans; D017578:Immunoglobulin Class Switching; D051379:Mice; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D027041:Somatic Hypermutation, Immunoglobulin; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D017931:DNA Primers; D006657:Histones; D018832:Molecular Chaperones; D050505:Mutant Proteins; D011994:Recombinant Proteins; C100927:SUPT6H protein, human; C502250:Supt6 protein, mouse; D014157:Transcription Factors; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase