Change search
ReferencesLink to record
Permanent link

Direct link
Expression and recruitment of uracil-DNA glycosylase are regulated by E2A during antibody diversification
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Show others and affiliations
2014 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 60, no 1, 23-31 p.Article in journal (Refereed) Published
Abstract [en]

B-lymphocytes can modify their immunoglobulin (Ig) genes to generate specific antibodies with a new isotype and enhanced affinity against an antigen. Activation-induced cytidine deaminase (AID), which is positively regulated by the transcription factor E2A, is the key enzyme that initiates these processes by deaminating cytosine to uracil in Ig genes. Nuclear uracil-DNA glycosylase (UNG2) is subsequently required for uracil processing in the generation of high affinity antibodies of different isotypes. Here we show that the transcription factor E2A binds to the UNG2 promoter and represses UNG2 expression. Inhibition of E2A by binding of Ca2+-activated calmodulin alleviates this repression. Furthermore, we demonstrate that UNG2 preferentially accumulates in regions of the Ig heavy chain (IgH) gene containing AID hotspots. Calmodulin inhibition of E2A strongly enhances this UNG2 accumulation, indicating that it is negatively regulated by E2A as well. We show also that over-expression of E2A can suppress class switch recombination. The results suggest that E2A is a key factor in regulating the balance between AID and UNG2, both at expression and Ig targeting levels, to stimulate Ig diversification and suppress normal DNA repair processes. (c) 2014 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
2014. Vol. 60, no 1, 23-31 p.
Keyword [en]
B cells, Cell differentiation, Antibodies, Gene regulation, Transcription factors
National Category
Cell and Molecular Biology
URN: urn:nbn:se:umu:diva-90404DOI: 10.1016/j.molimm.2014.03.011ISI: 000336473200004OAI: diva2:733596
Available from: 2014-07-10 Created: 2014-06-23 Last updated: 2014-07-10Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Wallenius, AndersHauser, JannekGrundström, Thomas
By organisation
Department of Molecular Biology (Faculty of Medicine)
In the same journal
Molecular Immunology
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 140 hits
ReferencesLink to record
Permanent link

Direct link