Study of transcriptional cycle regulation via in vitro reconstitution

2016 Fiscal Year Final Research Report

• Project Area: Integral understanding of the mechanism of transcription cycle through quantitative, high-resolution approaches
• Project/Area Number: 24118003
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• 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): 大熊 芳明 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (70192515) ; 広瀬 豊 富山大学, 大学院医学薬学研究部(薬学), 准教授 (00218851)
• Project Period (FY): 2012-06-28 – 2017-03-31
• Keywords: クロマチン / ヒストン / 癌化 / メディエーター / TFIIE

Outline of Final Research Achievements

We found that histone H2A Thr 120 is phosphorylated in human cancer cell lines and proved that H2A Thr 120 phosphorylation is catalyzed by hVRK1. By knocking down VRK1, cyclin D1 was found to be down-regulated by loss of H2A Thr120 phosphorylation and increased H2A Lys119 ubiquitylation of its promoter region resulted in impaired cell growth. In vivo, we identified that histone H2A is hyper-phosphorylated with up-regulated cyclin D1 in human gastrointestinal tract cancer tissues. In vitro, mutated H2A Thr 120 Asp that mimics phosphorylation transformed NIH3T3 cells. This suggested that histone H2A Thr 120 hyper-phosphorylation by hVRK1 causes inappropriate gene expression including up-regulated cyclin D1, resulting in carcinogenesis.
Ohkuma et al determined TFIIE structure using X-ray crystallography. They demonstrated that Mediator is functioning by activating essential genes using kinase module.

Free Research Field

生化学