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

关键词：

D O I：

暂无

中图分类号：

学科分类号：

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.

引用

共 43 条

[1] Muramatsu M(2000)Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme Cell 102 553-63
[2] Liang G(2013)RNA editing of hepatitis B virus transcripts by activation-induced cytidine deaminase Proc Natl Acad Sci USA 110 2246-51
[3] Gordon MS(2003)Somatic hypermutation of the B cell receptor genes B29 (Igbeta, CD79b) and mb1 (Igalpha, CD79a) Proc Natl Acad Sci USA 100 4126-31
[4] Robbiani DF(2009)AID produces DNA double-strand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations Mol Cell 36 631-41
[5] Meng FL(2014)Convergent transcription at intragenic super-enhancers targets AID-initiated genomic instability Cell 159 1538-48
[6] Qian J(2014)B cell super-enhancers and regulatory clusters recruit AID tumorigenic activity Cell 159 1524-37
[7] Jeevan-Raj BP(2011)Epigenetic tethering of AID to the donor switch region during immunoglobulin class switch recombination J Exp Med 208 1649-60
[8] Xu Z(2010)14-3-3 adaptor proteins recruit AID to 5′-AGCT-3′-rich switch regions for class switch recombination Nat Struct Mol Biol 17 1124-35
[9] Romanello M(2016)Histone H3.3 promotes IgV gene diversification by enhancing formation of AID-accessible single-stranded DNA EMBO J 35 1452-64
[10] Wang L(2006)AID-dependent histone acetylation is detected in immunoglobulin S regions J Exp Med 203 215-26

← 1 2 3 4 5 →