DNA Methylation Dynamics of Germinal Center B Cells Are Mediated by AID

被引：89

作者：

Dominguez, Pilar M. ^{[1
]}

Teater, Matt ^{[1
,2
]}

Chambwe, Nyasha ^{[2
,3
]}

Kormaksson, Matthias ^{[4
]}

Redmond, David ^{[2
,3
]}

Ishii, Jennifer ^{[5
]}

Vuong, Bao ^{[6
]}

Chaudhuri, Jayanta ^{[6
]}

Melnick, Ari ^{[1
]}

Vasanthakumar, Aparna ^{[7
]}

Godley, Lucy A. ^{[7
]}

Papavasiliou, F. Nina ^{[8
]}

Elemento, Olivier ^{[2
,3
]}

Shaknovich, Rita ^{[1
,9
,10
]}

机构：

[1] Weill Cornell Med Coll, Div Hematol & Oncol, New York, NY 10065 USA

[2] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10065 USA

[3] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA

[4] IBM Res, BR-22290240 Rio De Janeiro, Brazil

[5] Weill Cornell Med Coll, Epigen Core Facil, New York, NY 10065 USA

[6] Mem Sloan Kettering Canc Ctr, Immunol Program, Gerstner Sloan Kettering Grad Sch, New York, NY 10065 USA

[7] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[8] Rockefeller Univ, Labs Lymphocyte Biol & Mol Parasitol, New York, NY 10065 USA

[9] Weill Cornell Med Coll, Dept Pathol, New York, NY 10065 USA

[10] Weill Cornell Med Coll, Lab Med, New York, NY 10065 USA

来源：

CELL REPORTS | 2015年 / 12卷 / 12期

基金：

美国国家科学基金会;

关键词：

CYTIDINE DEAMINASE AID; DOUBLE-STRAND BREAKS; GENOME; IDENTIFICATION; RECOMBINATION; HYPERMUTATION; ACTIVATION; MECHANISMS; GENERATION; EXPRESSION;

D O I：

10.1016/j.celrep.2015.08.036

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Changes in DNA methylation are required for the formation of germinal centers (GCs), but the mechanisms of such changes are poorly understood. Activation-induced cytidine deaminase (AID) has been recently implicated in DNA demethylation through its deaminase activity coupled with DNA repair. We investigated the epigenetic function of AID in vivo in germinal center B cells (GCBs) isolated from wildtype (WT) and AID-deficient (Aicda(-/-)) mice. We determined that the transit of B cells through the GC is associated with marked locus-specific loss of methylation and increased methylation diversity, both of which are lost in Aicda(-/-) animals. Differentially methylated cytosines (DMCs) between GCBs and naive B cells (NBs) are enriched in genes that are targeted for somatic hypermutation (SHM) by AID, and these genes form networks required for B cell development and proliferation. Finally, we observed significant conservation of AID-dependent epigenetic reprogramming between mouse and human B cells.

引用

页码：2086 / 2098

页数：13

共 58 条

[1] Base-Pair Resolution DNA Methylation Sequencing Reveals Profoundly Divergent Epigenetic Landscapes in Acute Myeloid Leukemia [J].

Akalin, Altuna ;

Garrett-Bakelman, Francine E. ;

Kormaksson, Matthias ;

Busuttil, Jennifer ;

Zhang, Lu ;

Khrebtukova, Irina ;

Milne, Thomas A. ;

Huang, Yongsheng ;

Biswas, Debabrata ;

Hess, Jay L. ;

Allis, C. David ;

Roeder, Robert G. ;

Valk, Peter J. M. ;

Lowenberg, Bob ;

Delwel, Ruud ;

Fernandez, Hugo F. ;

Paietta, Elisabeth ;

Tallman, Martin S. ;

Schroth, Gary P. ;

Mason, Christopher E. ;

Melnick, Ari ;

Figueroa, Maria E. .

PLOS GENETICS, 2012, 8 (06)

[2] Identification of Early Replicating Fragile Sites that Contribute to Genome Instability [J].

Barlow, Jacqueline H. ;

Faryabi, Robert B. ;

Callen, Elsa ;

Wong, Nancy ;

Malhowski, Amy ;

Chen, Hua Tang ;

Gutierrez-Cruz, Gustavo ;

Sun, Hong-Wei ;

McKinnon, Peter ;

Wright, George ;

Casellas, Rafael ;

Robbiani, Davide F. ;

Staudt, Louis ;

Fernandez-Capetillo, Oscar ;

Nussenzweig, Andre .

CELL, 2013, 152 (03) :620-632

[3] 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

[4] DNA methylation patterns and epigenetic memory [J].

Bird, A .

GENES & DEVELOPMENT, 2002, 16 (01) :6-21

[5] New effector functions and regulatory mechanisms of BCL6 in normal and malignant lymphocytes [J].

Bunting, Karen L. ;

Melnick, Ari M. .

CURRENT OPINION IN IMMUNOLOGY, 2013, 25 (03) :339-346

[6] ENUMERATION AND CHARACTERIZATION OF DJH STRUCTURES IN MOUSE FETAL LIVER [J].

CHANG, Y ;

PAIGE, CJ ;

WU, GE .

EMBO JOURNAL, 1992, 11 (05) :1891-1899

[7] Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors [J].

Cobaleda, Cesar ;

Jochum, Wolfram ;

Busslinger, Meinrad .

NATURE, 2007, 449 (7161) :473-U8

[8] The AID/APOBEC family of nucleic acid mutators [J].

Conticello, Silvestro G. .

GENOME BIOLOGY, 2008, 9 (06)

[9] Aberration in DNA Methylation in B-Cell Lymphomas Has a Complex Origin and Increases with Disease Severity [J].

De, Subhajyoti ;

Shaknovich, Rita ;

Riester, Markus ;

Elemento, Olivier ;

Geng, Huimin ;

Kormaksson, Matthias ;

Jiang, Yanwen ;

Woolcock, Bruce ;

Johnson, Nathalie ;

Polo, Jose M. ;

Cerchietti, Leandro ;

Gascoyne, Randy D. ;

Melnick, Ari ;

Michor, Franziska .

PLOS GENETICS, 2013, 9 (01)

[10] Processive DNA Demethylation via DNA Deaminase-Induced Lesion Resolution [J].

Franchini, Don-Marc ;

Chan, Chun-Fung ;

Morgan, Hugh ;

Incorvaia, Elisabetta ;

Rangam, Gopinath ;

Dean, Wendy ;

Santos, Fatima ;

Reik, Wolf ;

Petersen-Mahrt, Svend K. .

PLOS ONE, 2014, 9 (07)

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