A comprehensive analysis of the effects of the deaminase AID on the transcriptome and methylome of activated B cells

被引：44

作者：

Fritz, Eric L. ^{[1
,2
]}

Rosenberg, Brad R. ^{[1
,3
]}

Lay, Kenneth ^{[1
,2
]}

Mihailovic, Aleksandra ^{[4
]}

Tuschl, Thomas ^{[4
]}

Papavasiliou, F. Nina ^{[1
]}

机构：

[1] Rockefeller Univ, Lab Lymphocyte Biol, New York, NY 10021 USA

[2] Rockefeller Univ, Rockefeller Grad Program, New York, NY 10021 USA

[3] Rockefeller Univ, John C Whitehead Presidential Fellows Program, New York, NY 10021 USA

[4] Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10021 USA

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 07期

基金：

美国国家卫生研究院;

关键词：

INDUCED CYTIDINE DEAMINASE; DNA METHYLATION; SEQUENCING REVEALS; ANTIBODY DIVERSIFICATION; SOMATIC HYPERMUTATION; GENOME; DEMETHYLATION; PLURIPOTENT; BREAKS; 5-METHYLCYTOSINE;

D O I：

10.1038/ni.2616

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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(-/-)), wildtype 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.

引用

页码：749 / +

页数：8

共 55 条

[1] Zebrafish AID is capable of deaminating methylated deoxycytidines [J].

Abdouni, Hala ;

King, Justin J. ;

Suliman, Mussa ;

Quinlan, Matthew ;

Fifield, Heather ;

Larijani, Mani .

NUCLEIC ACIDS RESEARCH, 2013, 41 (10) :5457-5468

[2] Systematic identification of edited microRNAs in the human brain [J].

Alon, Shahar ;

Mor, Eyal ;

Vigneault, Francois ;

Church, George M. ;

Locatelli, Franco ;

Galeano, Federica ;

Gallo, Angela ;

Shomron, Noam ;

Eisenberg, Eli .

GENOME RESEARCH, 2012, 22 (08) :1533-1540

[3]

[Anonymous], 2012, R LANG ENV STAT COMP, p3

[4] A critical role for AID in the initiation of reprogramming to induced pluripotent stem cells [J].

Bhutani, Nidhi ;

Decker, Matthew N. ;

Brady, Jennifer J. ;

Bussat, Rose T. ;

Burns, David M. ;

Corbel, Stephane Y. ;

Blau, Helen M. .

FASEB JOURNAL, 2013, 27 (03) :1107-1113

[5] Reprogramming towards pluripotency requires AID-dependent DNA demethylation [J].

Bhutani, Nidhi ;

Brady, Jennifer J. ;

Damian, Mara ;

Sacco, Alessandra ;

Corbel, Stephane Y. ;

Blau, Helen M. .

NATURE, 2010, 463 (7284) :1042-U57

[6] DNA Methylation Dynamics during In Vivo Differentiation of Blood and Skin Stem Cells [J].

Bock, Christoph ;

Beerman, Isabel ;

Lien, Wen-Hui ;

Smith, Zachary D. ;

Gu, Hongcang ;

Boyle, Patrick ;

Gnirke, Andreas ;

Fuchs, Elaine ;

Rossi, Derrick J. ;

Meissner, Alexander .

MOLECULAR CELL, 2012, 47 (04) :633-647

[7] Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase [J].

Bransteitter, R ;

Pham, P ;

Scharff, MD ;

Goodman, MF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :4102-4107

[8] Transcription-targeted DNA deamination by the AID antibody diversification enzyme [J].

Chaudhuri, J ;

Tian, M ;

Khuong, C ;

Chua, K ;

Pinaud, E ;

Alt, FW .

NATURE, 2003, 422 (6933) :726-730

[9] Genome-wide Translocation Sequencing Reveals Mechanisms of Chromosome Breaks and Rearrangements in B Cells [J].

Chiarle, Roberto ;

Zhang, Yu ;

Frock, Richard L. ;

Lewis, Susanna M. ;

Molinie, Benoit ;

Ho, Yu-Jui ;

Myers, Darienne R. ;

Choi, Vivian W. ;

Compagno, Mara ;

Malkin, Daniel J. ;

Neuberg, Donna ;

Monti, Stefano ;

Giallourakis, Cosmas C. ;

Gostissa, Monica ;

Alt, Frederick W. .

CELL, 2011, 147 (01) :107-119

[10] Thymine DNA Glycosylase Is Essential for Active DNA Demethylation by Linked Deamination-Base Excision Repair [J].

Cortellino, Salvatore ;

Xu, Jinfei ;

Sannai, Mara ;

Moore, Robert ;

Caretti, Elena ;

Cigliano, Antonio ;

Le Coz, Madeleine ;

Devarajan, Karthik ;

Wessels, Andy ;

Soprano, Dianne ;

Abramowitz, Lara K. ;

Bartolomei, Marisa S. ;

Rambow, Florian ;

Bassi, Maria Rosaria ;

Bruno, Tiziana ;

Fanciulli, Maurizio ;

Renner, Catherine ;

Klein-Szanto, Andres J. ;

Matsumoto, Yoshihiro ;

Kobi, Dominique ;

Davidson, Irwin ;

Alberti, Christophe ;

Larue, Lionel ;

Bellacosa, Alfonso .

CELL, 2011, 146 (01) :67-79

← 1 2 3 4 5 6 →