A cis-Acting Diversification Activator Both Necessary and Sufficient for AID-Mediated Hypermutation

被引：58

作者：

Blagodatski, Artem ^{[1
]}

Batrak, Vera ^{[1
]}

Schmidl, Sabine ^{[1
]}

Schoetz, Ulrike ^{[1
]}

Caldwell, Randolph B. ^{[1
]}

Arakawa, Hiroshi ^{[1
]}

Buerstedde, Jean-Marie ^{[1
]}

机构：

[1] Helmholtz Ctr Munich, Inst Mol Radiobiol, Neuherberg, Germany

来源：

PLOS GENETICS | 2009年 / 5卷 / 01期

基金：

俄罗斯基础研究基金会;

关键词：

B-CELL LINE; IMMUNOGLOBULIN GENE CONVERSION; CLASS SWITCH RECOMBINATION; LIGHT-CHAIN GENE; SOMATIC HYPERMUTATION; INTRON ENHANCER; DEAMINASE AID; REGION; MUTATION; GENOME;

D O I：

10.1371/journal.pgen.1000332

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Hypermutation of the immunoglobulin (Ig) genes requires Activation Induced cytidine Deaminase (AID) and transcription, but it remains unclear why other transcribed genes of B cells do not mutate. We describe a reporter transgene crippled by hypermutation when inserted into or near the Ig light chain (IgL) locus of the DT40 B cell line yet stably expressed when inserted into other chromosomal positions. Step-wise deletions of the IgL locus revealed that a sequence extending for 9.8 kilobases downstream of the IgL transcription start site confers the hypermutation activity. This sequence, named DIVAC for diversification activator, efficiently activates hypermutation when inserted at non-Ig loci. The results significantly extend previously reported findings on AID-mediated gene diversification. They show by both deletion and insertion analyses that cis-acting sequences predispose neighboring transcription units to hypermutation.

引用

页数：11

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