摘要：

Secondary Ig gene diversication relies on activation-induced cytidine deaminase (AID) to create U:G mismatches that are subsequently xed by mutagenic repair pathways. AID activity is focused to Ig loci by cis -regulatory DNA sequences named targeting elements. In this study, we show that in contrast to prevailing thought in the eld, the targeting elements in the chicken IGL locus are distinct from classical transcriptional enhancers. These mutational enhancer elements (MEEs) are required over and above transcription to recruit AID-mediated mutagenesis to Ig loci. We identied a small 222-bp fragment in the chicken IGL locus that enhances mutagenesis without boosting transcription, and this sequence represents a key component of an MEE. Lastly, MEEs are evolutionarily conserved among birds, both in sequence and function, and contain several highly conserved sequence modules that are likely involved in recruiting trans -acting targeting factors. We propose that MEEs represent a novel class of cis -regulatory elements for which the function is to control genomic integrity. The Journal of Immunology , 2011, 187: ctivation-induced cytidine deaminase (AID) is a DNA mutator enzyme that initiates the secondary Ab gene diversication processes somatic hypermutation (SHM), Ig gene conversion (GCV), and class-switch recombination (CSR) (1–3). AID converts cytosines to uracils in the context of ssDNA that is generated during transcription, and the resulting U:G mismatches are xed by direct replication or repaired by error-prone DNA repair pathways (4, 5). SHM and GCV are closely related and alter the nucleotide sequence in the VJ (or VDJ) exon of Ig genes, thus modifying Ab specicity. In contrast, CSR leaves the Ag-binding sites unaltered and swaps the C region from the

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