The regulatory machinery of histone methyltransferases ESET in normal liver and liver cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460977
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Chiba University
• Principal Investigator: Chiba Tetsuhiro 千葉大学, 医学(系)研究科(研究院), 講師 (00381583)
• Co-Investigator(Renkei-kenkyūsha): IWAMA ATSUSHI 千葉大学, 大学院医学研究院, 教授 (70244126)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 幹細胞

Outline of Final Research Achievements

Histone lysine methyltransferases, such as ESET and SUV39H1, regulate transcriptional repression through the formation of Histone H3 lysine 9 trimethylation (H3K9me3). In the loss-of-function assays for HCC cells, SUV39H1 knockdown but not ESET knockdown reduced H3K9me3 levels and impaired HCC cell growth and sphere formation. The expression levels of SUV39H1 but not those of ESET were significantly correlated with H3K9me3 levels in primary HCC samples. In addition, loss of ESET function in embryonic murine hepatic stem/progenitor cells derived from tamoxifen-inducible conditional knockout mice for ESET, severely impaired proliferation and self-renewal capability.
Our findings indicate that ESET plays an essential role in the maintenance of both the proliferative and self-renewal capacity of hepatic stem/progenitor cells but not in the tumorigenicity of HCC cells.

Free Research Field

肝臓病学