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Nature Communications
Article . 2013 . Peer-reviewed
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Nature Communications
Article
License: CC BY NC ND
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PubMed Central
Other literature type . 2013
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GANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy

Authors: Singh, Shailendra Kumar; Maeda, Kazuhiko; Eid, Mohammed Mansour Abbas; Almofty, Sarah Ameen; Ono, Masaya; Pham, Phuong; Goodman, Myron F.; +1 Authors

GANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy

Abstract

Somatic hypermutation in B cells is initiated by activation-induced cytidine deaminase-catalyzed C→U deamination at immunoglobulin variable regions. Here we investigate the role of the germinal centre-associated nuclear protein (GANP) in enhancing the access of activation-induced cytidine deaminase (AID) to immunoglobulin variable regions. We show that the nuclear export factor GANP is involved in chromatin modification at rearranged immunoglobulin variable loci, and its activity requires a histone acetyltransferase domain. GANP interacts with the transcription stalling protein Spt5 and facilitates RNA Pol-II recruitment to immunoglobulin variable regions. Germinal centre B cells from ganp-transgenic mice showed a higher AID occupancy at the immunoglobulin variable region, whereas B cells from conditional ganp-knockout mice exhibit a lower AID accessibility. These findings suggest that GANP-mediated chromatin modification promotes transcription complex recruitment and positioning at immunoglobulin variable loci to favour AID targeting.

Keywords

Cell Nucleus, Mice, Knockout, B-Lymphocytes, Immunoglobulin Variable Region, Intracellular Signaling Peptides and Proteins, Down-Regulation, Nuclear Proteins, Acetylation, DNA, Germinal Center, Models, Biological, Article, Nucleosomes, Histones, Mice, Acetyltransferases, Genetic Loci, Cytidine Deaminase, Gene Knockdown Techniques, Animals, Humans

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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
49
Top 10%
Top 10%
Top 10%
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gold