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Gain-of-function analysis of cis-acting diversification elements in DT40 cells.
Immunol. Cell Biol. 96, 948-957 (2018)
Publ. Version/Full Text
Research data
DOI
PMC
Activation-induced cytidine deaminase (AID) is required for the immunoglobulin diversification processes of somatic hypermutation, gene conversion and class-switch recombination. The targeting of AID's deamination activity is thought to be a combination of cis- and trans-acting elements, but has not been fully elucidated. Deletion analysis of putative proximal cis-regulatory motifs, while helpful, fails to identify additive versus cumulative effects, redundancy, and may create new motifs where none previously existed. In contrast, gain-of-function analysis can be more insightful with fewer of the same drawbacks and the output is a positive result. Here, we show five defined DNA regions of the avian Ig locus that are sufficient to confer events of hypermutation to a target gene. In our analysis, the essential cis-targeting elements fully reconstituted diversification of a transgene under heterologous promotion in the avian B-cell line DT40. Furthermore, to the best of our knowledge two of the five regions we report on here have not previously been described as individually having an influence on somatic hypermutation.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Activation-induced Cytosine Deaminase (aid Aicd) ; Cis-targeting Elements ; Dna Regulatory Motifs ; Immunoglobulin Diversification ; Somatic Hypermutation ; Transgene Diversification; Induced Cytidine Deaminase; Immunoglobulin Gene Conversion; Class Switch Recombination; Somatic Hypermutation; B-cells; Aid; Activation; Expression; Dna; Transcription
ISSN (print) / ISBN
0818-9641
e-ISSN
1440-1711
Journal
Immunology & cell biology
Quellenangaben
Volume: 96,
Issue: 9,
Pages: 948-957
Publisher
Springer
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Translational Metabolic Oncology (IDC-TMO)