Plasma cell differentiation is coupled to division-dependent DNA hypomethylation and gene regulation

被引：114

作者：

Barwick, Benjamin G. ^{[1
]}

Scharer, Christopher D. ^{[1
]}

Bally, Alexander P. R. ^{[1
]}

Boss, Jeremy M. ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA

来源：

NATURE IMMUNOLOGY | 2016年 / 17卷 / 10期

基金：

美国国家卫生研究院;

关键词：

GERMINAL CENTER B; METHYLATION ANALYSIS; SECRETING CELLS; SEQ DATA; TRANSCRIPTION; EXPRESSION; PROTEIN; LYMPHOCYTES; ACTIVATION; ELEMENTS;

D O I：

10.1038/ni.3519

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The epigenetic processes that regulate antibody-secreting plasma cells are not well understood. Here, analysis of plasma cell differentiation revealed DNA hypomethylation of 10% of CpG loci that were overrepresented at enhancers. Inhibition of DNA methylation enhanced plasma cell commitment in a cell-division-dependent manner. Analysis of B cells differentiating in vivo stratified by cell division revealed a fivefold increase in mRNA transcription coupled to DNA hypomethylation. Demethylation occurred first at binding motifs for the transcription factors NF-kappa B and AP-1 and later at those for the transcription factors IRF and Oct-2 and was coincident with activation and differentiation gene-expression programs in a cell-division-dependent manner. These data provide mechanistic insight into cell-division-coupled transcriptional and epigenetic reprogramming and suggest that DNA hypomethylation reflects the cis-regulatory history of plasma cell differentiation.

引用

页码：1216 / +

页数：13

共 66 条

[1] CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[2] Multiplexed Illumina sequencing libraries from picogram quantities of DNA [J].

Bowman, Sarah K. ;

Simon, Matthew D. ;

Deaton, Aimee M. ;

Tolstorukov, Michael ;

Borowsky, Mark L. ;

Kingston, Robert E. .

BMC GENOMICS, 2013, 14

[3] DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction [J].

Broeske, Ann-Marie ;

Vockentanz, Lena ;

Kharazi, Shabnam ;

Huska, Matthew R. ;

Mancini, Elena ;

Scheller, Marina ;

Kuhl, Christiane ;

Enns, Andreas ;

Prinz, Marco ;

Jaenisch, Rudolf ;

Nerlov, Claus ;

Leutz, Achim ;

Andrade-Navarro, Miguel A. ;

Jacobsen, Sten Eirik W. ;

Rosenbauer, Frank .

NATURE GENETICS, 2009, 41 (11) :1207-1215

[4] REXO2 Is an Oligoribonuclease Active in Human Mitochondria [J].

Bruni, Francesco ;

Gramegna, Pasqua ;

Oliveira, Jorge M. A. ;

Lightowlers, Robert N. ;

Chrzanowska-Lightowlers, Zofia M. A. .

PLOS ONE, 2013, 8 (05)

[5] Asymmetric T lymphocyte division in the initiation of adaptive immune responses [J].

Chang, John T. ;

Palanivel, Vikram R. ;

Kinjyo, Ichiko ;

Schambach, Felix ;

Intlekofer, Andrew M. ;

Banerjee, Arnob ;

Longworth, Sarah A. ;

Vinup, Kristine E. ;

Mrass, Paul ;

Oliaro, Jane ;

Killeen, Nigel ;

Orange, Jordan S. ;

Russell, Sarah M. ;

Weninger, Wolfgang ;

Reiner, Steven L. .

SCIENCE, 2007, 315 (5819) :1687-1691

[6] Lasting Antibody Responses Are Mediated by a Combination of Newly Formed and Established Bone Marrow Plasma Cells Drawn from Clonally Distinct Precursors [J].

Chernova, Irene ;

Jones, Derek D. ;

Wilmore, Joel R. ;

Bortnick, Alexandra ;

Yucel, Mesut ;

Hershberg, Uri ;

Allman, David .

JOURNAL OF IMMUNOLOGY, 2014, 193 (10) :4971-4979

[7] 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

[8] Histone H3K27ac separates active from poised enhancers and predicts developmental state [J].

Creyghton, Menno P. ;

Cheng, Albert W. ;

Welstead, G. Grant ;

Kooistra, Tristan ;

Carey, Bryce W. ;

Steine, Eveline J. ;

Hanna, Jacob ;

Lodato, Michael A. ;

Frampton, Garrett M. ;

Sharp, Phillip A. ;

Boyer, Laurie A. ;

Young, Richard A. ;

Jaenisch, Rudolf .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (50) :21931-21936

[9] Activation-Induced B Cell Fates Are Selected by Intracellular Stochastic Competition [J].

Duffy, Ken R. ;

Wellard, Cameron J. ;

Markham, John F. ;

Zhou, Jie H. S. ;

Holmberg, Ross ;

Hawkins, Edwin D. ;

Hasbold, Jhagvaral ;

Dowling, Mark R. ;

Hodgkin, Philip D. .

SCIENCE, 2012, 335 (6066) :338-341

[10] Epigenetics in human disease and prospects for epigenetic therapy [J].

Egger, G ;

Liang, GN ;

Aparicio, A ;

Jones, PA .

NATURE, 2004, 429 (6990) :457-463

← 1 2 3 4 5 6 7 →