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A comprehensive analysis of the effects of the deaminase AID on the transcriptome and methylome of activated B cells

机译:脱氨酶AID对活化B细胞转录组和甲基化组的影响的综合分析

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Beyond its well-characterized functions in antibody diversification, the cytidine deaminase AID can catalyze off-target DNA damage and has been hypothesized to edit RNA and mediate DNA demethylation. To comprehensively examine the effects of AID on the transcriptome and the pattern of DNA methylation ('methylome'), we analyzed AID-deficient (Aicda -/-), wild-type and AID-overexpressing activated B cells by high-throughput RNA sequencing (RNA-Seq) and reduced-representation bisulfite sequencing (RRBS). These analyses confirmed the known role of AID in immunoglobulin isotype switching and also demonstrated few other effects of AID on gene expression. Additionally, we detected no evidence of AID-dependent editing of mRNA or microRNA. Finally, the RRBS data did not support the proposed role for AID in regulating DNA methylation. Thus, despite evidence of its additional activities in other systems, antibody diversification seems to be the sole physiological function of AID in activated B cells.
机译:胞嘧啶脱氨酶AID除了在抗体多样化方面具有众所周知的功能外,还可以催化脱靶DNA损伤,并被认为可以编辑RNA并介导DNA脱甲基。为了全面检查AID对转录组和DNA甲基化模式('methylome')的影响,我们通过高通量RNA测序分析了AID缺失(Aicda-/-),野生型和AID过表达的活化B细胞(RNA-Seq)和还原表示亚硫酸氢盐测序(RRBS)。这些分析证实了AID在免疫球蛋白同种型转换中的已知作用,并且还证明了AID对基因表达的其他影响很少。此外,我们没有发现任何依赖AID的mRNA或microRNA编辑的证据。最后,RRBS数据不支持拟议的AID在调节DNA甲基化中的作用。因此,尽管有证据表明其在其他系统中具有额外的活性,但抗体多样化似乎是活化B细胞中AID的唯一生理功能。

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