Identification of pH-induced transcription factors governing pH stress adaptation

2023 Fiscal Year Final Research Report

• Project Area: Establishment of pH Biology
• Project/Area Number: 20H05788
• Research Category: Grant-in-Aid for Transformative Research Areas (B)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (III)
• Research Institution: Kyoto University
• Principal Investigator: Takakahashi Nobuaki 京都大学, 工学研究科, 准教授 (70604635)
• Co-Investigator(Kenkyū-buntansha): 圓岡 真宏 京都大学, 高等研究院, 特定助教 (70736412)
• Project Period (FY): 2020-10-02 – 2023-03-31
• Keywords: pH

Outline of Final Research Achievements

The primary objective of this study was to address one of the most crucial challenges in life sciences, which is the identification of pH-induced transcription factors, with the aim of revolutionizing the biological understanding of pH. Specifically, after identifying enhancer regions required for gene expression induction by low pH stimuli, we extensively identified proteins binding to these regions through mass spectrometry experiments, resulting in the discovery of approximately 400 candidate genes for pH-induced transcription factors. Moving forward, we plan to use CRISPR-Cas9 technology to disrupt each candidate gene and identify those whose response to pH stimuli is attenuated, thereby finalizing the pH-induced transcription factors.

Free Research Field

分子生物化学

Academic Significance and Societal Importance of the Research Achievements

酸化ストレス誘導型転写因子NRF2や低酸素ストレス誘導型転写因子HIFの発見が及ぼした歴史、またpHが司る生物学的枢要性・多様性を考えると、pH誘導型転写因子の同定により現代の生物学の常識を超えた新規生命現象が見えてくることは間違いなく、かつ多くの研究における源流になることが期待される。またpH異常は事実上すべての疾患に関わっていることが予想されるため、創薬の観点でも非常に重要な知見を得ることになる。