Structural elucidation of the multi-subunit interactions that establish the transcriptional unity mechanism

2023 Fiscal Year Final Research Report

• Project Area: Elucidation of the mechanisms of transcriptional unity by understanding spatiotemporal multifactorial interactions
• Project/Area Number: 21H05161
• Research Category: Grant-in-Aid for Transformative Research Areas (B)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (III)
• Research Institution: Yokohama City University
• Principal Investigator: SENGOKU Toru 横浜市立大学, 医学部, 准教授 (60576312)
• Project Period (FY): 2021-08-23 – 2024-03-31
• Keywords: クライオ電子顕微鏡 / エピジェネティクス / 転写 / 修復 / ユビキチン化

Outline of Final Research Achievements

Lysine ubiquitination of histone H2B regulates transcription elongation and DNA repair, contributing to cancer suppression. In this study, we solved the cryo-EM structure of the H2B ubiquitination enzyme Bre1 complex (comprising Bre1A/RNF20 and Bre1B/RNF40) bound to the nucleosome. The two RING domains bind to the acidic patch of the nucleosome and DNA, directing the E2 enzyme and ubiquitin near the target lysine. This structure, along with previous studies, suggests that the flexibility of nucleosomal DNA may regulate H2B ubiquitination. Mutant analysis showed that the Bre1A subunit recruits E2 and ubiquitin for H2B ubiquitination.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、ヒストンの翻訳後修飾がゲノム機能を制御する仕組みの一端を解明した。この成果は細胞の運命決定機構やDNA修復機構の深い理解につながる。また、Bre1Aはがん抑制因子として知られており、本研究はH2Bユビキチン化の異常が関与するがんの発症機構の理解やその診断法・治療法開発に有用な情報を与える。