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

Shailendra Kumar Singh, Kazuhiko Maeda, Mohammed Mansour Abbas Eid, Sarah Ameen Almofty, Masaya Ono, Phuong Pham, Myron F. Goodman and Nobuo Sakaguchi ()
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Shailendra Kumar Singh: Graduate School of Life Sciences, Kumamoto University
Kazuhiko Maeda: Graduate School of Life Sciences, Kumamoto University
Mohammed Mansour Abbas Eid: Graduate School of Life Sciences, Kumamoto University
Sarah Ameen Almofty: Graduate School of Life Sciences, Kumamoto University
Masaya Ono: National Cancer Center Research Institute
Phuong Pham: University of Southern California
Myron F. Goodman: University of Southern California
Nobuo Sakaguchi: Graduate School of Life Sciences, Kumamoto University

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: 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.

Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2823

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DOI: 10.1038/ncomms2823

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