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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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
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
ISSN (print) / ISBN
1553-7390
e-ISSN
1553-7404
Zeitschrift
PLoS Genetics
Quellenangaben
Band: 5,
Heft: 1,
Artikelnummer: e1000332
Verlag
Public Library of Science (PLoS)
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Molecular Radiation Biology (IMS)