Identification of KLF5 related three-dimensional genome structure

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09077
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka University
• Principal Investigator: Otsuka Masahisa 大阪大学, 大学院医学系研究科, 招へい教員 (20597455)
• Co-Investigator(Kenkyū-buntansha): 山本 浩文 大阪大学, 大学院医学系研究科, 教授 (30322184) ; 横山 雄起 大阪大学, 大学院医学系研究科, 助教 (60615714)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: KLF5 / 三次元ゲノム構造

Outline of Final Research Achievements

KLF5 is a transcription factor which is reported to be up-regulated in certain cancer types such as gastrointestinal adenocarcinoma and squamous cell carcinoma. In our previous studies, we showed that KLF5 protein was involved in the establishment and maintenance of three-dimensional genome structure.
In this study, we investigated the three-dimensional genome structure engaged by a transcription factor KLF5 protein using genome analysis techniques such as in vitro enChIP method to develop a new cancer therapy. Based on our results of KLF5 ChIP-sequencing and database analysis, we focused on gene A, which is associated with the malignancy and stemness of cancer. We found that the promoter region of gene A interacted with the promoter region of NR2F2 gene, which is reported to be highly expressed in various cancers. Our data also suggest that the expression of gene A and NR2F2 is coordinately regulated through the three-dimensional genome structure.

Free Research Field

消化器外科、腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

三次元ゲノム構造を介した遺伝子発現制御メカニズムは近年着目されており、三次元ゲノム構造を標的とした癌治療法は新たなアプローチとなりうる。
KLF5タンパクは消化器癌や扁平上皮癌などの種々の癌種で発現が亢進しており、幹細胞性との関連も報告されていることから有望な治療標的であり、本研究で取り組んだKLF5タンパクによって形作られる三次元ゲノム構造を介した遺伝子発現制御メカニズムの解明は新たな治療法の開発につながると考えられる。