Single particle dynamics of the NF-kB foci in the living cell nucleus

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22404
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Sako Yasushi 国立研究開発法人理化学研究所, 開拓研究本部, 主任研究員 (20215700)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: 転写調節

Outline of Final Research Achievements

Cellular gene expression is regulated by complex molecular assemblies, among which the super-enhancer (SE) is considered to play a major role by regulating collective gene expression. However, the details of its function and structure are unclear. In this study, we investigated the relationship between gene expression and formation of the NF-kB foci in the nucleus during differentiation of immune B cells.
The NF-kB foci co-localized with BRD4 protein and were reversibly resolved by hexanediol, suggesting that they are a transcription initiation site with a liquid-liquid phase-separated structure. We analyzed NF-kB accumulation and gene expression in detail using RNA-seq and RNA-FISH, and found that downstream of NF-kB, the gene transcriptions were highly cooperative and fluctuating. Especially, CD83 gene transcription fluctuated in correlation with NF-kB accumulation. Single-cell transcription analysis also suggested that CD83 expression is regulated by SE formation.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

生物の基本単位である細胞が、全体性・一貫性を保って環境に応答し変化して行くには、多くの遺伝子発現が協調して制御されることが必須であると考えられるが、その仕組みは不明な点が多い。我々は、免疫B細胞由来の培養細胞の細胞成熟過程で、NF-kBという代表的転写制御蛋白質が、核内に多数の集積点を作ることを発見した。この構造の性質と遺伝子発現の関係を研究し、CD83を含む特定の遺伝子群の協調的制御の様子から、それがスーパーエンハンサーと呼ばれる協調的遺伝子発現制御構造の一つである可能性を明らかにした。