Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites

被引：0
作者：
Virginia C. Rodríguez-Cortez
Paloma Martínez-Redondo
Francesc Català-Moll
Javier Rodríguez-Ubreva
Antonio Garcia-Gomez
Ganesh Poorani-Subramani
Laura Ciudad
Henar Hernando
Arantxa Pérez-García
Carlos Company
José M. Urquiza
Almudena R. Ramiro
Javier M. Di Noia
Alejandro Vaquero
Esteban Ballestar
机构：
[1] Chromatin and Disease Group,
[2] Cancer Epigenetics and Biology Programme (PEBC),undefined
[3] Bellvitge Biomedical Research Institute (IDIBELL),undefined
[4] Chromatin Biology Group,undefined
[5] Cancer Epigenetics and Biology Programme (PEBC),undefined
[6] Bellvitge Biomedical Research Institute (IDIBELL),undefined
[7] Institut de Recherches Cliniques de Montréal,undefined
[8] Division of Immunity and Viral Infections,undefined
[9] Division of Experimental Medicine,undefined
[10] Faculty of Medicine,undefined
[11] McGill University,undefined
[12] B Cell Biology Lab,undefined
[13] Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC),undefined
[14] Université de Montréal,undefined
[15] Department of Medicine,undefined
来源：
Scientific Reports | / 7卷
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摘要：
Activation-induced cytidine deaminase (AID) triggers antibody diversification in B cells by catalysing deamination and subsequently mutating immunoglobulin (Ig) genes. Association of AID with RNA Pol II and occurrence of epigenetic changes during Ig gene diversification suggest participation of AID in epigenetic regulation. AID is mutated in hyper-IgM type 2 (HIGM2) syndrome. Here, we investigated the potential role of AID in the acquisition of epigenetic changes. We discovered that AID binding to the IgH locus promotes an increase in H4K20me3. In 293F cells, we demonstrate interaction between co-transfected AID and the three SUV4-20 histone H4K20 methyltransferases, and that SUV4-20H1.2, bound to the IgH switch (S) mu site, is replaced by SUV4-20H2 upon AID binding. Analysis of HIGM2 mutants shows that the AID truncated form W68X is impaired to interact with SUV4-20H1.2 and SUV4-20H2 and is unable to bind and target H4K20me3 to the Smu site. We finally show in mouse primary B cells undergoing class-switch recombination (CSR) that AID deficiency associates with decreased H4K20me3 levels at the Smu site. Our results provide a novel link between SUV4-20 enzymes and CSR and offer a new aspect of the interplay between AID and histone modifications in setting the epigenetic status of CSR sites.
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