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

Abstract 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 participatio...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9cd2b9c633a74c8184f98b09354dec72
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spelling	oai:doaj.org-article:9cd2b9c633a74c8184f98b09354dec722021-12-02T15:06:22ZActivation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites10.1038/s41598-017-07380-92045-2322https://doaj.org/article/9cd2b9c633a74c8184f98b09354dec722017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07380-9https://doaj.org/toc/2045-2322Abstract 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.Virginia C. Rodríguez-CortezPaloma Martínez-RedondoFrancesc Català-MollJavier Rodríguez-UbrevaAntonio Garcia-GomezGanesh Poorani-SubramaniLaura CiudadHenar HernandoArantxa Pérez-GarcíaCarlos CompanyJosé M. UrquizaAlmudena R. RamiroJavier M. Di NoiaAlejandro VaqueroEsteban BallestarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites
description	Abstract 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.
format	article
author	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
author_facet	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
author_sort	Virginia C. Rodríguez-Cortez
title	Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites
title_short	Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites
title_full	Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites
title_fullStr	Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites
title_full_unstemmed	Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites
title_sort	activation-induced cytidine deaminase targets suv4-20-mediated histone h4k20 trimethylation to class-switch recombination sites
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9cd2b9c633a74c8184f98b09354dec72
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Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites

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