PfGCN5 is essential for Plasmodium falciparum survival and transmission and regulates Pf H2B.Z acetylation and chromatin structure

Tang J, Yeoh LM, Grotz M, Goodman CD, Tang J, Nguyen HH, Yu C, Pareek K, Mcpherson F, Cozijnsen A, Hustadt SA, Josling GA, Day KP, Schulz D, Mcfadden GI, De Koning-Ward TF, Petter M, Duffy MF

Publication Type: Journal article

Journal

Nucleic Acids Research Oxford University Press

Book Volume: 53

Article Number: gkaf218

Journal Issue: 6

DOI: 10.1093/nar/gkaf218

Abstract

Plasmodium falciparum causes most malaria deaths. Its developmental transitions and environmental adaptation are partially regulated by epigenetic mechanisms. Plasmodium falciparum GCN5 (PfGCN5) is an epigenetic regulator that acetylates lysines and can also bind to acetylated lysine residues on histones via its bromodomain (BRD). Here, we showed that PfGCN5 was essential for parasite transmission and survival in human blood and mosquitoes. PfGCN5 regulated genes important for metabolism and development and its BRD was required at euchromatic gene promoters for their proper expression and for acetylation of the variant histone Pf H2B.Z. However, PfGCN5 was most abundant in heterochromatin and loss of the PfGCN5 BRD de-repressed heterochromatic genes and increased levels of acetylated Pf H2B.Z in heterochromatin. The PfGCN5 BRD-binding compound L-45 phenocopied deletion of the PfGCN5 BRD, identifying PfGCN5 as a promising drug target for BRD inhibitors. Thus, PfGCN5 appears to directly contribute to activating euchromatic promoters, but PfGCN5 is also critical for maintaining repressive heterochromatin structure.

Authors with CRIS profile

Myriam Grotz Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Kapil Pareek Lehrstuhl für Mikrobiologie und Infektionsimmunologie Samuel Andre Hustadt Medizinische Fakultät

Additional Organisation(s)

Graduiertenkolleg 2740/1 - Microenvironmental, Metabolic and Microbial Signals Regulationg Immune Cell-Pathogen Interactions (ImmunoMicroTope 2)

Involved external institutions

Deakin University AU Australia (AU) Peter Doherty Institute AU Australia (AU) The University of Melbourne AU Australia (AU) Harvey Mudd College US United States (USA) (US)

How to cite

APA:

Tang, J., Yeoh, L.M., Grotz, M., Goodman, C.D., Tang, J., Nguyen, H.H.,... Duffy, M.F. (2025). PfGCN5 is essential for Plasmodium falciparum survival and transmission and regulates Pf H2B.Z acetylation and chromatin structure. Nucleic Acids Research, 53(6). https://doi.org/10.1093/nar/gkaf218

MLA:

Tang, Jingyi, et al. "PfGCN5 is essential for Plasmodium falciparum survival and transmission and regulates Pf H2B.Z acetylation and chromatin structure." Nucleic Acids Research 53.6 (2025).

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