Jumonji-C demethylase 2 interacts with a nucleosome component to modulate chromatin state in Plasmodium falciparum

Abstract

Epigenetic regulation plays a central role in the developmental control and antigenic variation of Plasmodium falciparum, yet the functions of many chromatin-modifying enzymes remain poorly understood. Here, we investigated the role of the putative Jumonji C (JmjC) domain-containing enzyme PfJmjC2 (PF3D7_0602800) in maintaining chromatin organization and histone modification balance during the asexual blood stages of the parasite. Using a conditional glmS ribozyme-mediated knockdown system, we achieved a [~]70% reduction in PfJmjC2 transcript and protein levels, which resulted in a marked delay in DNA replication and intraerythrocytic development. Immunoprecipitation assays revealed that PfJmjC2 physically interacts with histone H2A, suggesting an association with the nucleosome core. Upon PfJmjC2 depletion, the balance of epigenetic marks was disrupted, indicating a shift toward a more compact and transcriptionally repressed chromatin state. MNase-ChIP-PCR analysis further showed that PfJmjC2 associates with nucleosome-dense regions, including var gene promoters, although its reduction did not alter var gene transcription or switching patterns. Together, these findings indicate that PfJmjC2 contributes to chromatin organization and nucleosome stability rather than direct transcriptional control, highlighting its potential role in maintaining chromatin compaction and epigenetic homeostasis in P. falciparum.