The role of chromatin organization and histone modifications in genome integrity network

• Project/Area Number: 26440007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Molecular biology
• Research Institution: University of Miyazaki
• Principal Investigator: Takami Yasunari 宮崎大学, 医学部, 准教授 (80236356)
• Co-Investigator(Renkei-kenkyūsha): NISHITOU HIDEKI 宮崎大学, 医学部, 教授 (00332627)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ヒストン / クロマチン / ヘテロクロマチン / DNA修復 / クロマチン動態

Outline of Final Research Achievements

RbAp46/48 family, histone chaperone, is evolutionarily conserved WD40 proteins, which are involved in various chromatin-metabolizing process, but their in vivo functional relevance is yet unclear. To examine the biological role of pRbAp48, we generated a conditional RbAp48-knokout cells. Depletion of RbAp48 led to delayed S phase progression associated with slow DNA synthesis and nascent nucleosome formation, followed by cell death. Prior to cell death, these cells exhibited aberrant mitosis such as highly condensed and abnormal chromosome alignment on the metaphase plate, leading to chromosome missegregation, concomitant with loss of HP1 association to pericentromere and elevated levels of acetylation and sligtly decreased levels of methylation, specifically at Lys-9 residue of histone H3. These results suggest that RbAp48 plays an important role for the chromosome stability in proper organization of heterochromatin structure through the regulation of epigenetic mark.

Research Products

• [Journal Article] Acetylation of histone H4 lysine 5 and 12 is required for CENP-A deposition into centromeres (2016)
  • Author(s): Shang, W. H. Hori, T. Westhorpe, F. G. Godek, K. M. Toyoda, A. Misu, S. Monma, N. Ikeo, K. Carroll, C. W. Takami, Y. Fujiyama, A. Kimura, H. Straight, A. F. Fukagawa, T.
  • Journal Title: Nature communications Volume: 7 Issue: 1 Pages: 13465-13465
  • DOI: 10.1038/ncomms13465
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] RbAp48 is essential for viability of vertebrate cells and plays a role in chromosome stability (2016)
  • Author(s): Pasjan Satrimafitrah, Hirak Kumar Barman, Ahyar Ahmad, Hideki Nishitoh, Tatsuo Nakayama, Tatsuo Fukagawa & Yasunari Takami
  • Journal Title: Chromosome Research Volume: 24 Issue: 2 Pages: 161-173
  • DOI: 10.1007/s10577-015-9510-8
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] GCN5 is involved in regulation of immunoglobulin heavy chain gene expression in immature B cells. (2014)
  • Author(s): Kikuchi H., Nakayama M., Kuribayashi F., Imajoh-Ohmi S., Nishitoh H., Takami Y., Nakayama T.
  • Journal Title: Gene Volume: 544 Issue: 1 Pages: 19-24
  • DOI: 10.1016/j.gene.2014.04.030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Protein kinase Cθ gene expression is oppositely regulated by GCN5 and EBF1 in immature B cells. (2014)
  • Author(s): Kikuchi H, Nakayama M, Kuribayashi F, Imajoh-Ohmi S, Nishitoh H, Takami Y, Nakayama T
  • Journal Title: FEBS Lett Volume: 588 Issue: 9 Pages: 1739-1742
  • DOI: 10.1016/j.febslet.2014.03.025
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] GCN5 is essential for IRF-4 gene expression followed by transcriptional activation of Blimp-1 in immature B cells. (2014)
  • Author(s): Kikuchi H, Nakayama M, Kuribayashi F, Imajoh-Ohmi S, Nishitoh H, Takami Y, Nakayama T.
  • Journal Title: J Leukoc Biol Volume: 95 Issue: 3 Pages: 399-404
  • DOI: 10.1189/jlb.0413232
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Protective role of Naa60, a cellular acetyltransferase, in chemically induced DNA damage (2014)
  • Author(s): Pasjan SatrimaFitrah, 西頭 英起, 高見 恭成
  • Organizer: 第３７回分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27