Jumonji-C domain containing demethylase 1 is critical for heterochromatin organization in Plasmodium falciparum

Despite the central importance of epigenetic regulation in enabling adaptation and pathogenicity of malaria parasites, mechanisms controlling heterochromatin distribution in Plasmodium falciparum are poorly understood. Here, we identified P. falciparum Jumonji C domain-containing histone demethylase 1, PfJmjC1, as a key regulator of heterochromatin. Parasites lacking PfJmjC1 are viable in vitro but display slightly reduced multiplication rates compared to wild type parasites. Interestingly, PfJmjC1 depletion leads to major heterochromatin reorganization, involving de novo heterochromatin formation over non-essential, GC-rich euchromatic genes and reduction of heterochromatin at some chromosome ends, eventually altering the 3D genome architecture. Importantly, this heterochromatin reorganization results in the deregulation of cell surface antigen expression and failure of parasites to induce gametocyte production in response to nutrient deprivation. Collectively, our findings highlight the crucial role of PfJmjC1 in regulating heterochromatin distribution and life cycle progression in this deadly pathogen.