ＡＩＤによるゲノム再構成に伴うクロマチン制御

2014 Fiscal Year Annual Research Report

• Project/Area Number: 24590352
• Research Institution: Kyoto University
• Principal Investigator: BEGUM NasimAra 京都大学, 医学(系)研究科(研究院), 准教授 (80362507)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: AID / SHM / CSR / H3K4me3 / FACT / SPT6 / BRD4 / UNG

Outline of Annual Research Achievements

AID induced genomic rearrangement of transcriptionally active IgH locus takes places via complex DNA cleavage and recombination processes. The aim of the study was to identify transcription-coupled chromatin features involved in AID induced SHM and CSR.

It revealed that the AID target loci that undergo DNA cleavage are enriched with SPT6, FACT, H3K4me3 and H3.3. While SPT6 and FACT are key histone chaperones required for the epigenetic integrity of the IgH locus, SPT6 is specifically required for the AID locus. In contrast, H4 acetyl reader BRD4 is required to promote recruitment of UNG and DNA repair proteins in the IgH locus. Therefore, the target loci associated DNA break and repair phase specific chromatin proteins are crucial in AID induced genomic instability regulation.

Research Products

• [Journal Article] Identification of DNA cleavage- and recombination-specific hnRNP co-factors for Activation-induced cytidine deaminase. (2015)
  • Author(s): Hu W, Begum NA, Mondal S, Stanlie A and Honjo T
  • Journal Title: Proc Natl Acad Sci U S A Volume: in press Pages: in press
  • DOI: doi:10.1073/pnas.1506167112
  • Peer Reviewed
• [Journal Article] Chromatin reader Brd4 functions in Ig class switching as a repair complex adaptor of nonhomologous end-joining (2014)
  • Author(s): Stanlie A, Yousif AS, Akiyama H, Honjo T and Begum NA.
  • Journal Title: Molecular Cell Volume: 55(1) Pages: 97-110
  • DOI: doi: 10.1016/j.molcel.2014.05.018
  • Peer Reviewed
• [Journal Article] Opinion: uracil DNA glycosylase (UNG) plays distinct and non-canonical roles in somatic hypermutation and class switch recombination. (2014)
  • Author(s): Yousif AS, Stanlie A, Begum NA and Honjo T
  • Journal Title: International Immunology Volume: 26(10) Pages: 575-578
  • DOI: doi: 10.1093/intimm/dxu071
  • Peer Reviewed
• [Presentation] Co-factors of AID function: hnRNP K for DNA cleavage and hnRNP L for recombination (2014)
  • Author(s): Wenjun Hu, Nasim Begum and Tasuku Honjo
  • Organizer: The 43rd Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kyoto
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Chromatin reader Brd4 functions in Ig class switching as a repair complex adaptor of nonhomologous end-joining (2014)
  • Author(s): Andre Stanlie, Ashraf S. Yousif, Honjo Tasuku and Nasim A. Begum
  • Organizer: The 43rd Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kyoto
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Differential regulation of S region hypermutation and class switch recombination by non-canonical functions of uracil DNA glycosylase (2014)
  • Author(s): Ashraf S. Yousif, Andre Stanlie, Samiran Mondal, Honjo Tasuku and Nasim A. Begum
  • Organizer: The 43rd Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kyoto
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Analysis of Top1-chromatin complex reveals the mechanism of AID induced genomic instability (2014)
  • Author(s): Afzal Husain, Nasim A. Begum, Maki Kobayashi and Tasuku Honjo
  • Organizer: Gordon Research Conference: Genomic Instability-Mechanisms
  • Place of Presentation: Hong Kong
  • Year and Date: 2014-07-06 – 2014-07-11
• [Book] Molecular Biology of B Cells. Chapter18 (Molecular mechanism of AID function) (2015)
  • Author(s): Begum NA Nagaoka H, Kobayashi M and Honjo T
  • Total Pages: 305-344 (Chapter18)
  • Publisher: ESLVIER, Academic Press