title: A comprehensive analysis of the effects of the deaminase AID on the transcriptome and methylome of activated B cells.
abstract: Beyond its well-characterized functions in antibody diversification, the cytidine deaminase AID can catalyze off-target DNA damage and has been hypothesized to edit RNA and mediate DNA demethylation. To comprehensively examine the effects of AID on the transcriptome and the pattern of DNA methylation ('methylome'), we analyzed AID-deficient (Aicda(-/-)), wild-type and AID-overexpressing activated B cells by high-throughput RNA sequencing (RNA-Seq) and reduced-representation bisulfite sequencing (RRBS). These analyses confirmed the known role of AID in immunoglobulin isotype switching and also demonstrated few other effects of AID on gene expression. Additionally, we detected no evidence of AID-dependent editing of mRNA or microRNA. Finally, the RRBS data did not support the proposed role for AID in regulating DNA methylation. Thus, despite evidence of its additional activities in other systems, antibody diversification seems to be the sole physiological function of AID in activated B cells.
authors.affiliation: Laboratory of Lymphocyte Biology, The Rockefeller University, New York, New York, USA. efritz@rockefeller.edu
authors.forename: Eric L
authors.initials: EL
authors.lastname: Fritz
authors.forename: Brad R
authors.initials: BR
authors.lastname: Rosenberg
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lay
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Mihailović
authors.forename: Thomas
authors.initials: T
authors.lastname: Tuschl
authors.forename: F Nina
authors.initials: FN
authors.lastname: Papavasiliou
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003564:Cytidine Deaminase / Q000276:immunology*; D005260:Female; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D017422:Sequence Analysis, DNA; D027041:Somatic Hypermutation, Immunoglobulin / Q000276:immunology*; D059467:Transcriptome / Q000276:immunology*
chemical_list: D007132:Immunoglobulin Isotypes; D035683:MicroRNAs; D012333:RNA, Messenger; D003564:Cytidine Deaminase