Ig 类别转换重组中重叠的激活诱导胞苷脱氨酶热点基序。
Overlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination.
机构信息
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
出版信息
Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11584-9. doi: 10.1073/pnas.1018726108. Epub 2011 Jun 27.
Abstract
Ig class-switch recombination (CSR) is directed by the long and repetitive switch regions and requires activation-induced cytidine deaminase (AID). One of the conserved switch-region sequence motifs (AGCT) is a preferred site for AID-mediated DNA-cytosine deamination. By using somatic gene targeting and recombinase-mediated cassette exchange, we established a cell line-based CSR assay that allows manipulation of switch sequences at the endogenous locus. We show that AGCT is only one of a family of four WGCW motifs in the switch region that can facilitate CSR. We go on to show that it is the overlap of AID hotspots at WGCW sites on the top and bottom strands that is critical. This finding leads to a much clearer model for the difference between CSR and somatic hypermutation.
摘要
免疫球蛋白类别转换重组（CSR）由长而重复的转换区指导，并需要激活诱导的胞嘧啶脱氨酶（AID）。转换区的一个保守序列基序（AGCT）是 AID 介导的 DNA-胞嘧啶脱氨酶的首选位点。通过使用体细胞基因靶向和重组酶介导的盒交换，我们建立了基于细胞系的 CSR 测定法，该方法允许在内源性基因座上操纵转换序列。我们表明，AGCT 只是转换区中四个 WGCW 基序家族中的一个，可促进 CSR。我们接着表明，关键是在顶部和底部链上的 WGCW 位点上的 AID 热点的重叠。这一发现为 CSR 和体细胞高频突变之间的差异提供了一个更清晰的模型。
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