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
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DOI：
10.1073/pnas.1104423108
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发表时间：
2011-05-10
影响因子：
11.1
通讯作者：
Honjo, Tasuku
中科院分区：
文献类型：
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作者：
Okazaki, Il-mi;Okawa, Katsuya;Honjo, Tasuku
激活诱导的胞苷脱氨酶（AID）被证明是必不可少的，足以诱导IG基因座的两个遗传改变：类转换重组（CSR）和体细胞超突变（SHM）。然而，单分子AID如何差异调节CSR和SHM仍然是未知的。在这里，我们确定Spt6作为艾滋病相互作用蛋白的酵母双杂交筛选和免疫沉淀，然后通过质谱。Spt 6的敲低导致B细胞中内源性IG基因座和成纤维细胞中人工底物的CSR严重减少。相反，Spt 6的敲低没有减少，但略有增强SHM在人工基质中的B细胞，表明Spt 6是AID诱导CSR所需的，但不是SHM。这些结果表明Spt6参与了AID对CSR和SHM的差异调节。
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.