Elucidation of epigenomic regulation by chromosome segregation factor and identification of novel therapeutic target for leukemia

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03690
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Chiba University
• Principal Investigator: Hoshii Takayuki 千葉大学, 大学院医学研究院, 講師 (20464042)
• Co-Investigator(Kenkyū-buntansha): 金田 篤志 千葉大学, 大学院医学研究院, 教授 (10313024) ; 荒木 喜美 熊本大学, 生命資源研究・支援センター, 教授 (90211705)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 転写制御 / エピゲノム / 白血病

Outline of Final Research Achievements

The H3K4 methyltransferase SETD1A is one of MLL family members in vertebrate, but our study indicated the essential role of non-catalytic function for cell survival and cell proliferation in leukemia as well as other cancer cells. Here we demonstrated the possible roles of BuGZ as a transcriptional regulator for the SETD1A-dependent gene expression. BuGZ is known as an essential factor for chromosomal segregation but the knockdown of BuGZ induced apoptosis without showing the abnormality in chromosomal segregation in leukemia cells. We also observed the significant downregulation of DNA repair pathway-associated genes, which are known to be regulated by SETD1A, in BuGZ knockdown cells. BuGZ are localized at both TSS and enhancer region. These results suggested that BuGZ is a potential upstream regulator of SETD1A and a new therapeutic target for leukemia.

Free Research Field

血液腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究では白血病細胞の治療標的となりうる新規機能性タンパク質の解析を実施し、これまでに既に報告されていた機能とは全く異なる役割を見出した。染色体分配機構はがん細胞の継続的な細胞増殖に必須であるが、その際に働くタンパク質は細胞分裂以外でも重要な役割を担っていることが明らかとなった。このようなタンパク質を治療標的とすることは、増殖期のがんだけでなく、休止状態のがんの根絶にも効果を発揮することが期待される。