Abstract
SummaryMalaria parasites undergo a complex life cycle in the human host and the mosquito vector. The ApiAP2 family of DNA-binding proteins plays a dominant role in parasite development and life cycle progression. Most ApiAP2 factors studied to date act as transcription factors regulating stage-specific gene expression. Here, we characterized an ApiAP2 factor in Plasmodium falciparum that we termed PfAP2-HC. We demonstrate that PfAP2-HC specifically binds to heterochromatin throughout the genome. Intriguingly, PfAP2-HC does not bind DNA in vivo and recruitment of PfAP2-HC to heterochromatin is independent of its DNA-binding domain but strictly dependent on heterochromatin protein 1. Furthermore, our results suggest that PfAP2-HC functions neither in the regulation of gene expression nor in heterochromatin formation or maintenance. In summary, our findings reveal PfAP2-HC as a core component of heterochromatin in malaria parasites and identify unexpected properties and substantial functional divergence among the members of the ApiAP2 family of regulatory proteins.
Highlights
The apicomplexan parasite Plasmodium falciparum is the main cause of severe malaria worldwide, with the majority of the estimated 405,000 malarial deaths in 2018 attributed to this pathogen (WHO, 2019)
We demonstrate that PfAP2-HC binds to heterochromatin throughout the genome
Our results suggest that PfAP2-HC functions neither in the regulation of gene expression nor in heterochromatin formation or maintenance
Summary
The apicomplexan parasite Plasmodium falciparum is the main cause of severe malaria worldwide, with the majority of the estimated 405,000 malarial deaths in 2018 attributed to this pathogen (WHO, 2019). Heterochromatin is found at subtelomeric regions on all 14 chromosomes and in some chromosome internal islands and is characterized by the binding of heterochromatin protein 1 (PfHP1) to the histone modification histone 3 lysine 9 trimethylation (H3K9me3) (Flueck et al, 2009; Fraschka et al, 2018; Lopez-Rubio et al, 2009; Perez-Toledo et al, 2009; Salcedo-Amaya et al, 2009) These PfHP1/ H3K9me3-demarcated heterochromatic domains cover over 400 genes in total (approximately 8% of all protein-coding genes in the genome) (Flueck et al, 2009; Fraschka et al, 2018).
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