The mechanism for cell onocogenesis by chromosome-translocated chromatin remodeling factors

2009 Fiscal Year Final Research Report

• Project/Area Number: 17013018
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: University of Tsukuba
• Principal Investigator: NAGATA Kyosuke University of Tsukuba, 大学院・人間総合科学研究科, 教授 (40180492)
• Co-Investigator(Kenkyū-buntansha): TAKEUCHI Kaoru 筑波大学, 大学院・人間総合科学研究科, 准教授 (00192162) ; OKUWAKI Mitsuru 筑波大学, 大学院・人間総合科学研究科, 准教授 (50322699)
• Project Period (FY): 2005 – 2009
• Keywords: 遺伝子 / 癌 / 分子生物学 / 染色体転座 / 転写 / クロマチン / 細胞死 / 細胞周期

Research Abstract

The aim of this study is to clarify the mechanism of oncogesis by TAF-I-CAN generated by chromosomal translocation and associated with undifferentiated acute myeloma. In TAF-I-CAN transgenic mice that we constructed, haemopoietic cell differentiation was blocked. When TAF-I-CAN in the cell that had been once transformed by TAF-I-CAN was eliminated, some oncogenic phenotypes were not cancelled, suggesting that an epigenetic change(s) is involved in cell transformation by TAF-I-CAN. TAF-I-CAN was found to inhibit NF-κB- and CBP-mediated transcription by their being mislocalized and squelched, respectively, by TAF-I-CAN. In addition, we found the possibility that RAG proteins and their cryptic signal sequences are involved in translocation for generation of TEL-AML1.

Research Products

• [Journal Article] Epigenetic control of rDNA loci in response to intracellular energy status. (2008)
  • Author(s): Murayama A, Omori K, Fujimura A, Minami H, Yasuzawa-Tanaka K, Kuroda T, Oie S, Daitoku H, Okuwaki M, Nagata K, Fukamizu A, Kimura K, Shimizu T, Yanagisawa J.
  • Journal Title: Cell 133 Pages: 627-639
• [Journal Article] Impairment of erythroid and megakaryocytic differentiation by a leukemia-associated and t(9;9)-derived fusion gene product (2007)
  • Author(s): Saito S, Nouno K, Shimizu R, Yamamoto M, Nagata K.
  • Journal Title: SET/TAF-I β-CAN/Nup214. J. Cell. Physiol. 214 Pages: 322-333
• [Journal Article] Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2 (2006)
  • Author(s): Jin C, Kato K, Chimura T, Yamasaki T, Nakade K, Murata T, Li H, Pan J, Zhao M, Sun K, Chiu R, Ito T, Nagata K, Horikoshi M, Yokoyama K.
  • Journal Title: Nature Structural & Molecular Biology 13 Pages: 331-338
• [Presentation] Molecular and pysiological roles of nucleolar histone chaperones. (2009)
  • Author(s): Nagata K, Kato K, Murano K.
  • Organizer: The 24th Naito Conference on Nuclear Dynamics and RNA.
  • Place of Presentation: Sapporo
  • Year and Date: 20090623-20090626
• [Presentation] Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2 (2006)
  • Author(s): Jin C, Kato K, Chimura T, Yamasaki T, Nakade K, Murata T, Li H, Pan J, Zhao M, Sun K, Chiu R, Ito T, Nagata K, Horikoshi M, Yokoyama K.
  • Organizer: Nature Structural & Molecular Biology
  • Year and Date: 20060000
• [Book] Nuclear Dynamics-Molecular Biology and Visualozation of the Nucleus-. (2006)
  • Author(s): Nagata K, Takeyasu K.
  • Total Pages: 279
  • Publisher: Springer
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/basicmed/infectionbiology/virology/Site_2/Welcome.html