DNA methylation dynamics of germinal center B cells are mediated by AID Journal Article
| Authors: | Dominguez, P. M.; Teater, M.; Chambwe, N.; Kormaksson, M.; Redmond, D.; Ishii, J.; Vuong, B.; Chaudhuri, J.; Melnick, A.; Vasanthakumar, A.; Godley, L. A.; Papavasiliou, F. N.; Elemento, O.; Shaknovich, R. |
| Article Title: | DNA methylation dynamics of germinal center B cells are mediated by AID |
| Abstract: | 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 wild-type (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. © 2015 The Authors. |
| Keywords: | human cell; nonhuman; protein function; cell proliferation; animal cell; mouse; gene targeting; cell maturation; protein depletion; molecular dynamics; gene locus; in vivo study; wild type; dna methylation; b lymphocyte; germinal center; somatic hypermutation; activation induced cytidine deaminase; dna; epigenetics; cell isolation; gene regulatory network; cell transport; nuclear reprogramming; human; male; female; priority journal; article |
| Journal Title: | Cell Reports |
| Volume: | 12 |
| Issue: | 12 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2015-09-29 |
| Start Page: | 2086 |
| End Page: | 2098 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2015.08.036 |
| PROVIDER: | scopus |
| PMCID: | PMC4591215 |
| PUBMED: | 26365193 |
| DOI/URL: | |
| Notes: | Export Date: 2 November 2015 -- Source: Scopus |
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