Schematic representation of transcriptional activity of episomal promoters in transfection experiments.

<p>The string of nucleosomes represents chromosomal genes, whereas the circle represents an episome. Colored lines or boxes represent a promoter. (<b>A</b>) Promoter sequences placed in an episome recapitulate correct temporal expression. Orange and blue represent a ring stage–specific promoter and a late stage–specific promoter, respectively. (<b>B</b>) The transcriptional status of clonally variant promoters often does not coincide with the state of the endogeneous promoter. Possible states for endogenous and episomal promoters are represented. See <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002943#ppat-1002943-box001" target="_blank">Box 1</a> for details.</p

Schematic representation of processes in parasite biology that involve chromatin changes.

<p>(<b>A</b>) CVGE. Expression dynamics of a representative clonally variant gene. In a clonal population, stochastic switches between the active and silenced states of the gene result in transcriptional heterogeneity upon long-term growth. The active state is associated with activating histone PTMs (e.g., H3K9ac, green marks), whereas the silenced state is associated with repressive histone PTMs (e.g., H3K9me3, red marks). Subcloning followed by short-term growth results in populations of parasites that predominantly maintain the same transcriptional state as the single parasite from which they are derived, demonstrating epigenetic inheritance. (<b>B</b>) Asexual blood cycle progression. The three stretches of chromatin represent a gene expressed only in ring stages, trophozoites, or schizonts, respectively. Hypothetical stage-specific transcription factors (represented by ovals) control expression of the genes by acting on regulatory elements in the promoter sequences (colored DNA). Some histone PTMs are associated with active transcription (green marks), and global changes in chromatin organization occur at specific stages (e.g., higher nucleosome density in schizonts). It is unlikely that these modifications are stably transmitted from one generation to the next because they change during each cycle. (<b>C</b>) Adaptation via directed transcriptional responses. A change in the environment is sensed and via signal transduction (colored circles) results in a directed transcriptional response, which can operate via changes in chromatin structure (e.g., deposition of activating histone PTMs). Only if the chromatin changes and transcriptional status are maintained after the external signal disappears, is there epigenetic transmission of information (red star). To date, there is no well-described pathway in <i>P. falciparum</i> that involves sensing external conditions followed by a directed transcriptional response, but here we propose a conceptual framework to determine whether there is epigenetic inheritance of transcriptional states if such a pathway is ever identified.</p