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A cis-acting diversification activator both necessary and sufficient for AID-mediated hypermutation.
PLoS Genet. 5:e1000332 (2009)
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.
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8.883
1.120
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
AID; B cell; DT40; enhancer; gene conversion; immunoglobulin; somatic hypermutation; transcription; B-CELL LINE; IMMUNOGLOBULIN GENE CONVERSION; CLASS SWITCH RECOMBINATION; LIGHT-CHAIN GENE; SOMATIC HYPERMUTATION; INTRON ENHANCER; DEAMINASE AID; REGION; MUTATION; GENOME
Language
english
Publication Year
2009
HGF-reported in Year
0
ISSN (print) / ISBN
1553-7390
e-ISSN
1553-7404
Journal
PLoS Genetics
Quellenangaben
Volume: 5,
Issue: 1,
Article Number: e1000332
Publisher
Public Library of Science (PLoS)
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Radiation Biology (IMS)
PSP Element(s)
G-500400-001
PubMed ID
19132090
WOS ID
000266221100015
Scopus ID
59249094658
Erfassungsdatum
2009-09-21