Chromatin remodeling and Induction of pluripotency via Sox2/TBP complex

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04044
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Nagasaki University
• Principal Investigator: ITO Takashi 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90306275)
• Co-Investigator(Kenkyū-buntansha): 中川 武弥 長崎大学, 医歯薬学総合研究科(医学系), 助教 (50363502) ; 米田 光宏 長崎大学, 医歯薬学総合研究科(医学系), 講師 (80508367) ; 今村 優子 長崎大学, 医歯薬学総合研究科(医学系), 特任研究員 (50610937)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: クロマチン / SOX2 / TBP / リプログラミング

Outline of Final Research Achievements

It has been discovered that Reprogramming of somatic cells achieved by combination of the four transcription factors Oct4, Sox2, Klf4, and c-Myc. However detailed mechanisms of this reprograming remained to be clarified. Recently we identify unique SOX2 complex including stoichiometric amount of TBP without TAFs. SOX2/TBP Complex plays role in chromatin assembly. In addition, SOX2/TBP facilitated chromatin remodeling around promoter region of both RNA Pol II and Pol I, resulting in their transcriptional activation in vitro. Both SOX2 and TBP bound to core promoter or enhancer region of both RNA Pol II and Pol I. Knockdown of SOX2 or TBP resulted in decreased rDNA and OCT3/4 expression together with diminished their binding to core promoter and enhancer region in vivo. These results indicated unique complex including SOX2 and TBP plays a role both in Pol I and Pol II transcription.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

Oct3/4, Sox2, Klf4, cMycによる分化細胞から多能性幹細胞へのリプログラミングは再生医学領域への応用が期待され社会的にもインパクトの大きい領域である。実際に細胞核内で引き起こされる現象にはまだまだ未知の部分が多い。今回の実験によりSox2/TBP Complexはクロマチン構造変換能を有することを明らかにし、リプログラミングとエピジェネティクスの接点を明らかにしていく上で重要な発見である。詳細な機能の解明によりリプログラミングを含む再生医学領域に貢献できると考える。