Epigenetics in Plasmodium: what do we really know?

In the burgeoning field of Plasmodium gene expression, there are--to borrow some famous words from a former U.S. Secretary of Defense--"known knowns, known unknowns, and unknown unknowns." This is in itself an important achievement, since it is only in the past decade that facts have begun to move from the third category into the first. Nevertheless, much remains in the middle ground of known or suspected "unknowns." It is clear that the malaria parasite controls vital virulence processes such as host cell invasion and cytoadherence at least partly via epigenetic mechanisms, so a proper understanding of epigenetic transcriptional control in this organism should have great clinical relevance. Plasmodium, however, is an obligate intracellular parasite: it operates not in a vacuum but rather in the complicated context of its metazoan hosts. Therefore, as valuable data about the parasite's basic epigenetic machinery begin to emerge, it becomes increasingly important to relate in vitro studies to the situation in vivo. This review will focus upon the challenge of understanding Plasmodium epigenetics in an integrated manner, in the human and insect hosts as well as the petri dish.