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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Shailendra Kumar Singh & Kazuhiko Maeda & Mohammed Mansour Abbas Eid & Sarah Ameen Almofty & Masaya Ono & Phuong Pham & Myron F. Goodman & Nobuo Sakaguchi, 2013. "GANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy," Nature Communications, Nature, vol. 4(1), pages 1-12, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2823
    DOI: 10.1038/ncomms2823
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