Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation
| Autor: | Hisaaki Taniguchi, Kiyotsugu Yoshikawa, Shun-ichiro Iemura, Katsuya Okawa, Shimpei Kawamoto, Il-mi Okazaki, Hitoshi Nagaoka, Maki Kobayashi, Reiko Shinkura, Tasuku Honjo, Tohru Natsume, Yoko Kitawaki |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Immunoprecipitation
Somatic hypermutation chemical and pharmacologic phenomena Cell Line Histones Mice Cytidine Deaminase Two-Hybrid System Techniques medicine Animals Humans Protein Interaction Domains and Motifs Fibroblast DNA Primers Sequence Deletion B-Lymphocytes Gene knockdown Multidisciplinary Base Sequence biology Cytidine deaminase Biological Sciences Immunoglobulin Class Switching Molecular biology Recombinant Proteins Histone medicine.anatomical_structure Immunoglobulin class switching Gene Knockdown Techniques Chaperone (protein) biology.protein Mutant Proteins Somatic Hypermutation Immunoglobulin Molecular Chaperones Transcription Factors |
| Zdroj: | Proceedings of the National Academy of Sciences. 108:7920-7925 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1104423108 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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