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Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation
- Source :
- Proceedings of the National Academy of Sciences. 108:7920-7925
- Publication Year :
- 2011
- Publisher :
- Proceedings of the National Academy of Sciences, 2011.
-
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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 108
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....66d265feec72b5775d18c3bea11122ae