2. Academic Validation
  3. Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation

Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation

  • Proc Natl Acad Sci U S A. 2011 May 10;108(19):7920-5. doi: 10.1073/pnas.1104423108.
Il-mi Okazaki 1,  Katsuya Okawa,  Maki Kobayashi,  Kiyotsugu Yoshikawa,  Shimpei Kawamoto,  Hitoshi Nagaoka,  Reiko Shinkura,  Yoko Kitawaki,  Hisaaki Taniguchi,  Tohru Natsume,  Shun-Ichiro Iemura,  Tasuku Honjo
Affiliations

Affiliation

  • 1 Department of Immunology and Genomic Medicine, Frontier Technology Center, Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
PMID: 21518874 DOI: 10.1073/pnas.1104423108
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.

Figures