| Histone H2A and H2B are monoubiquitinated at AID-targeted loci. | |
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MedLine Citation:
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PMID: 20661291 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Somatic hypermutation introduces base substitutions into the rearranged and expressed immunoglobulin (Ig) variable regions to promote immunity. This pathway requires and is initiated by the Activation Induced Deaminase (AID) protein, which deaminates cytidine to produce uracils and UG mismatches at the Ig genes. Subsequent processing of uracil by mismatch repair and base excision repair factors contributes to mutagenesis. While selective for certain genomic targets, the chromatin modifications which distinguish hypermutating from non-hypermutating loci are not defined. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that AID-targeted loci in mammalian B cells contain ubiquitinated chromatin. Chromatin immunoprecipitation (ChIP) analysis of a constitutively hypermutating Burkitt's B cell line, Ramos, revealed the presence of monoubiquitinated forms of both histone H2A and H2B at two AID-associated loci, but not at control loci which are expressed but not hypermutated. Similar analysis using LPS activated primary murine splenocytes showed enrichment of the expressed V(H) and Sgamma3 switch regions upon ChIP with antibody specific to AID and to monoubiquitinated H2A and H2B. In the mechanism of mammalian hypermutation, AID may interact with ubiquitinated chromatin because confocal immunofluorescence microscopy visualized AID colocalized with monoubiquitinated H2B within discrete nuclear foci. CONCLUSIONS/SIGNIFICANCE: Our results indicate that monoubiquitinated histones accompany active somatic hypermutation, revealing part of the histone code marking AID-targeted loci. This expands the current view of the chromatin state during hypermutation by identifying a specific nucleosome architecture associated with somatic hypermutation. |
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Authors:
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Glen M Borchert; Nathaniel W Holton; Kevin A Edwards; Laura A Vogel; Erik D Larson |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-07-16 |
Journal Detail:
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Title: PloS one Volume: 5 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2010 |
Date Detail:
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Created Date: 2010-07-27 Completed Date: 2010-10-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e11641 Citation Subset: IM |
Affiliation:
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School of Biological Sciences, Illinois State University, Normal, Illinois, United States of America. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cell Line, Tumor Cells, Cultured Chromatin / metabolism Chromatin Immunoprecipitation Cytidine Deaminase / metabolism* Histones / metabolism* Humans Mice Microscopy, Confocal Microscopy, Fluorescence Polymerase Chain Reaction Ubiquitination / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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R15CA137608/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chromatin; 0/Histones; EC 3.5.4.5/Cytidine Deaminase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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