DNA methyltransferase 1 and DNA methylation patterning contribute to germinal center B-cell differentiation
作者： Rita Shaknovich , Leandro Cerchietti , Lucas Tsikitas , Matthias Kormaksson , Subhajyoti De
DOI: 10.1182/BLOOD-2011-06-357996
关键词:
摘要: The phenotype of germinal center (GC) B cells includes the unique ability to tolerate rapid proliferation and mutagenic actions activation induced cytosine deaminase (AICDA). Given importance epigenetic patterning in determining cellular phenotypes, we examined DNA methylation role methyltransferases formation GCs. profiling revealed a marked shift GC versus resting/naive cells. This included significant differential 235 genes, with concordant inverse changes gene expression affecting most notably genes NFkB MAP kinase signaling pathways. were predominantly hypomethylated compared naive AICDA binding sites highly overrepresented among loci. also exhibited greater heterogeneity than Among (DNMTs), only DNMT1 was significantly up-regulated Dnmt1 hypomorphic mice displayed deficient treatment methyltransferase inhibitor decitabine resulted failure form GCs after immune stimulation. Notably, animals showed evidence increased damage, suggesting dual roles for double strand break repair.
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Rita Shaknovich, Maria E. Figueroa, Ari Melnick, HELP (HpaII tiny fragment enrichment by ligation-mediated pcr) assay for dna methylation profiling of primary normal and malignant b lymphocytes Methods of Molecular Biology. ,vol. 632, pp. 191- 201 ,(2010) , 10.1007/978-1-60761-663-4_12
Christian Popp, Wendy Dean, Suhua Feng, Shawn J. Cokus, Simon Andrews, Matteo Pellegrini, Steven E. Jacobsen, Wolf Reik, Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by Aid deficiency Nature. ,vol. 463, pp. 1101- 1105 ,(2010) , 10.1038/NATURE08829
Man Liu, David G. Schatz, Balancing AID and DNA repair during somatic hypermutation Trends in Immunology. ,vol. 30, pp. 173- 181 ,(2009) , 10.1016/J.IT.2009.01.007
José I. Martín-Subero, Markus Kreuz, Marina Bibikova, Stefan Bentink, Ole Ammerpohl, Eliza Wickham-Garcia, Maciej Rosolowski, Julia Richter, Lidia Lopez-Serra, Esteban Ballestar, Hilmar Berger, Xabier Agirre, Heinz-Wolfram Bernd, Vincenzo Calvanese, Sergio B. Cogliatti, Hans G. Drexler, Jian-Bing Fan, Mario F. Fraga, Martin L. Hansmann, Michael Hummel, Wolfram Klapper, Bernhard Korn, Ralf Küppers, Roderick A. F. MacLeod, Peter Möller, German Ott, Christiane Pott, Felipe Prosper, Andreas Rosenwald, Carsten Schwaenen, Dirk Schübeler, Marc Seifert, Benjamin Stürzenhofecker, Michael Weber, Swen Wessendorf, Markus Loeffler, Lorenz Trümper, Harald Stein, Rainer Spang, Manel Esteller, David Barker, Dirk Hasenclever, Reiner Siebert, , New insights into the biology and origin of mature aggressive B-cell lymphomas by combined epigenomic, genomic, and transcriptional profiling Blood. ,vol. 113, pp. 2488- 2497 ,(2009) , 10.1182/BLOOD-2008-04-152900
Irina Velichutina, Rita Shaknovich, Huimin Geng, Nathalie A. Johnson, Randy D. Gascoyne, Ari M. Melnick, Olivier Elemento, EZH2-mediated epigenetic silencing in germinal center B cells contributes to proliferation and lymphomagenesis Blood. ,vol. 116, pp. 5247- 5255 ,(2010) , 10.1182/BLOOD-2010-04-280149
Andrea Hermann, Rachna Goyal, Albert Jeltsch, The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites. Journal of Biological Chemistry. ,vol. 279, pp. 48350- 48359 ,(2004) , 10.1074/JBC.M403427200
Alberto Martin, Philip D. Bardwell, Caroline J. Woo, Manxia Fan, Marc J. Shulman, Matthew D. Scharff, Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas. Nature. ,vol. 415, pp. 802- 806 ,(2002) , 10.1038/NATURE714
E. L. Fritz, F. N. Papavasiliou, Cytidine deaminases: AIDing DNA demethylation? Genes & Development. ,vol. 24, pp. 2107- 2114 ,(2010) , 10.1101/GAD.1963010
Nidhi Bhutani, Jennifer J. Brady, Mara Damian, Alessandra Sacco, Stéphane Y. Corbel, Helen M. Blau, Reprogramming towards pluripotency requires AID-dependent DNA demethylation Nature. ,vol. 463, pp. 1042- 1047 ,(2010) , 10.1038/NATURE08752
Virginia G de Yébenes, Almudena R Ramiro, None, Activation-induced deaminase: light and dark sides Trends in Molecular Medicine. ,vol. 12, pp. 432- 439 ,(2006) , 10.1016/J.MOLMED.2006.07.001