Analysis of molecular mechanism involved in 3D genome structure in the progression of malignant lymphoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08370
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyoto University
• Principal Investigator: Miyazaki Kazuko 京都大学, 医生物学研究所, 研究員 (00311811)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ゲノム構造

Outline of Final Research Achievements

Using our mouse model of malignant lymphoma (Id2/Id3 dKO), we not only compared normal and lymphoma cells, but also examined gene expression, epigenetic changes and genomic structural change during the progression from the activated/precancerous state to lymphoma cells. In the precancerous state, activation of enhancers like super-enhancers, which amplify the expression of target genes, were induced but was not accompanied by changes in 3D genome structure, including TADs and chromatin compartments. On the other hand, with the oncogenic transformation of cells, the activity of enhancers and other factors were conversely reduced, but the genomic structure, including changes in TAD structure, was greatly altered, suggesting that a specific gene expression program is triggered. Further analysis is required to determine how these chromatin changes are induced and how they contribute to the regulation of expression of tumor suppressor genes and other genes.

Free Research Field

遺伝子発現制御

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、悪性リンパ腫の自然発症モデルマウスを用いることで、正常細胞と癌細胞を比較するのみでなく、正常細胞が活性化・前癌状態からがん細胞へと進展する過程での遺伝子発現制御を解析したものであり、 がん進展のメカニズムの理解につながる社会的意義があると思われる。また、生体内における細胞腫特異的な遺伝子発現制御の理解という学術的に非常に重要な課題の解明に貢献するものである。