2024-03-29T15:50:42Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/51012022-10-14T12:47:14Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
00925njm 22002777a 4500
dc
Rodriguez-Cortez, Virginia C.
author
Martinez-Redondo, Paloma
author
Catala-Moll, Francesc
author
Rodriguez-Ubreva, Javier
author
Garcia-Gomez, Antonio
author
Poorani-Subramani, Ganesh
author
Ciudad, Laura
author
Hernando, Henar
author
Perez-Garcia, Arantxa
author
Company, Carlos
author
Urquiza, Jose M.
author
Ramiro, Almudena R
author
Di Noia, Javier M.
author
Vaquero, Alejandro
author
Ballestar, Esteban
author
2017
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.
Sci Rep. 2017; 7(1):7594
2045-2322
http://hdl.handle.net/20.500.12105/5101
28790320
10.1038/s41598-017-07380-9
Scientific Reports
DOUBLE-STRAND BREAKS
SOMATIC HYPERMUTATION
SUPER-ENHANCERS
RECRUIT AID
B-CELLS
DNA
METHYLATION
REGIONS
DEMETHYLATION
REPAIR
Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites