Protein landscape of the chromatin domains in the malaria parasite Plasmodium falciparum.

Epigenetic regulation is essential for development and adaptation across eukaryotes. However, a comprehensive overview of the molecular framework of chromatin-mediated regulation, particularly in non-model organisms, is lacking. Here, we present a systematic proteomic characterization of the chromatin domains in P. falciparum, an ancient human pathogen with a unique genome composition and epigenetic blueprint. We adapted and employed three proximity-labeling approaches to provide a high-confidence and comprehensive proteome of heterochromatin, euchromatin, and (peri)centromeric chromatin comprising 214 proteins, including both expected and new chromatin components. Characterization of 20 proteins validated our approach and uncovered (1) a protein influencing parasite transmission, (2) complexes relevant for histone variant exchange and chromatin-RNA interactions, and (3) the so-far believed-to-be-absent spindle assembly checkpoint and the corresponding Bub1-like kinase. This study hence offers a reference proteome of the chromatin domains and a resource to uncover novel chromatin biology.