Molecular analysis of γ1, γ3, and α class switch recombination junctions in APOBEC3-deficient mice using high-throughput sequencing

摘要

Activation-induced deaminase(AID)is required for immunoglobulin(Ig)class switch recombination(CSR),in which the constant(C)μgene of IgM is substituted with C_(γ),C_(ε),or C_(α),thereby generating IgG,IgE,and IgA antibodies,respectively,with new effector functions but the same antigenic specificity.1 AID targets specific DNA switch(S)regions preceding C regions except for Cδ.2 Sμis usually the donor region,while Sγ,ε,αare the acceptor regions.AID deaminates C into U on single-stranded DNA by targeting the WRCY(W=A/T,R=A/G,and Y=C/T)hot motif and,to a lesser extent,the SYC(S=G/C,Y=C/T)cold motif.3,4 AID is a member of the apolipoprotein B editing complex(APOBEC)family.Among APOBEC genes,a family of evolutionarily conserved cytidine deaminases,APOBEC3 is implicated in diverse cell functions including innate immunity against retroviruses.4 The DNA-editing APOBEC3 enzymes have recently attracted attention due to their involvement in cancer and potential applications in gene editing.5–7 While a single copy of each APOBEC3 gene is present in rodents,seven copies of each APOBEC3 gene are found in humans.