Abstract
The well-known and invidious pathology caused by malaria parasites (Plasmodium spp.) stems from the intraerythrocytic developmental cycle (IDC), which is the progressive invasion of erythrocytes by the merozoite form of the parasite followed by parasite growth, asexual replication, and lysis of the host cell liberating logarithmically greater numbers of infectious merozoites. Gene expression during the asexual IDC can largely be viewed as the result of an iterated transcriptional cascade predominantly orchestrated by members of the ApiAP2 family of transcription factors/chromatin regulators that is initiated upon sporozoite transformation in the hepatocyte [1]. However, parasite populations generated during this growth phase are far from homogeneous. Successful (even isogenic) parasite populations superimpose variation upon the basal transcriptional programme through bet hedging [2].
Highlights
Regulation of the var repertoire is achieved epigenetically, which is achieved through histone N-terminal tail modification, creating silenced zones of facultative heterochromatin [6] that are gathered together in a filamentous actin-controlled process [8], perhaps facilitating their communal regulation
Such absolute silence might be achieved through specialised epigenetic regulation and a dedicated, and not wholly conserved, SETdomain containing methyltransferase (PfSet 2 or PfSetvs) that methylates H3K36 in P. falciparum and is associated with var gene silencing
That is essential for gametocyte maturation and contains an AP2-G binding site in its promoter region [21]
Summary
Citation: Waters AP (2016) Epigenetic Roulette in Blood Stream Plasmodium: Gambling on Sex. PLoS Pathog 12(2): e1005353. doi:10.1371/journal. ppat.1005353 Funding: The author's laboratory is supported by grants from the Wellcome Trust (083811) and the European Commission grant agreement 242095 (Evimalar). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The author has declared that no competing interests exist.
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