Set regulation in asexual and sexual Plasmodium parasites reveals a novel mechanism of stage‐specific expression

Abstract

SummaryTransmission of the malaria parasite depends on specialized gamete precursors (gametocytes) that develop in the bloodstream of a vertebrate host. Gametocyte/gamete differentiation requires controlled patterns of gene expression and regulation not only of stage and gender-specific genes but also of genes associated with DNA replication and mitosis. Once taken up by mosquito, male gametocytes undergo three mitotic cycles within few minutes to produce eight motile gametes. Here we analysed, in two Plasmodium species, the expression of SET, a conserved nuclear protein involved in chromatin dynamics. SET is expressed in both asexual and sexual blood stages but strongly accumulates in male gametocytes. We demonstrated functionally the presence of two distinct promoters upstream of the set open reading frame, the one active in all blood stage parasites while the other active only in gametocytes and in a fraction of schizonts possibly committed to sexual differentiation. In ookinetes both promoters exhibit a basal activity, while in the oocysts the gametocyte-specific promoter is silent and the reporter gene is only transcribed from the constitutive promoter. This transcriptional control, described for the first time in Plasmodium , provides a mechanism by which single-copy genes can be differently modulated during parasite development. In male gametocytes an overexpression of SET might contribute to a prompt entry and execution of S/M phases within mosquito vector.

Sexual development in Plasmodium parasites: knowing when it's time to commit

“…Although PfNAPS is also transcribed in asexual-stage parasites, the gene has two stage-specific promoters 81 . One promoter is active only in asexual parasites, whereas the other is only active in a small number of schizonts (potentially those that are committed to gametocytogenesis) and in male gametocytes.…”

Specific tagging of the egress-related osmiophilic bodies in the gametocytes of Plasmodium falciparum

“…A 1883 bp fragment, including the putative promoter region and 240 bp of pfg377 coding region, was amplified from 3D7 genomic DNA with primers p1 and p2 and cloned into the pHHMC*/3R0.5 plasmid [14], using SacII and XhoI restriction sites. DsRed gene was PCR amplified from plasmid pBac(3xP3RED)AgApy [15], with primers p3 and p4 and cloned in the same plasmid with XhoI and KpnI.…”

Expression of Exogenous Human Hepatic Nuclear Factor-1α by a Lentiviral Vector and Its Interactions withPlasmodium falciparumSubtilisin-Like Protease 2

“…Moreover, clarifying transcription regulation in the Plasmodium genome is onerous because of the genome's abnormal AT-richness [27,28]. Nonetheless, Plasmodium genes are organized similarly to those in eukaryotes and are also monocistronically transcribed [29-31], implying the presence of regulatory sequence elements flanking the coding regions [32,33]. For example, the region upstream to the Pf multidrug resistance gene can be induced at the transcriptional level by antimalarial drugs in chloroquine-sensitive parasites [34].…”