Set1-mediated H3K4 methylation is required for Candida albicans virulence by regulating intracellular level of reactive oxygen species

Jueun Kim, Shinae Park, Sohee Kwon, Eun Jin Lee, Jung Shin Lee

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Candida albicans is an opportunistic human fungal pathogen that exists in normal flora but can cause infection in immunocompromised individuals. The transition to pathogenic C. albicans requires a change of various gene expressions. Because histone-modifying enzymes can regulate gene expression, they are thought to control the virulence of C. albicans. Indeed, the absence of H3 lysine 4 (H3K4) methyltransferase Set1 has been shown to reduce the virulence of C. albicans; however, Set1-regulated genes responsible for this attenuated virulence phenotype remain unknown. Here, we demonstrated that Set1 positively regulates the expression of mitochondrial protein genes by methylating H3K4. In particular, levels of cellular mitochondrial reactive oxygen species (ROS) were higher in Δset1 than in the wild-type due to the defect of those genes’ expression. Set1 deletion also increases H2O2 sensitivity and prevents proper colony formation when interacting with macrophage in vitro, consistent with its attenuated virulence in vivo. Together, these findings suggest that Set1 is required to regulate proper cellular ROS production by positively regulating the expression of mitochondrial protein genes and subsequently sustaining mitochondrial membrane integrity. Consequently, C. albicans maintains proper ROS levels via Set1-mediated transcriptional regulation, thus establishing a rapid defense against external ROS generated by the host.

Original languageEnglish
Pages (from-to)2648-2658
Number of pages11
Issue number1
Publication statusPublished - 2021

Bibliographical note

Funding Information:
We thank Ali Shilatifard for providing the antibodies and Cornelius Clancy for kindly giving the Set1 deletion mutant. This work was supported by the National Research Foundation of Korea under Grant [No. NRF-2015R1D1A1A02061743; NRF-2018R1D1A1A02048280; and NRF-2020R1I1A3072234].

Publisher Copyright:
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.


  • Candida albicans
  • Set1
  • cellular ROS
  • h3k4 methyltransferase
  • virulence

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases


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