Chromatin modifications: implications in the regulation of gene expression inToxoplasma gondii

Abstract

SummaryThe apicomplexan Toxoplasma gondii completes its life cycle by successive processes of parasite differentiation that rely on a tight control of gene expression to ensure appropriate protein profiles on time. During the last 5 years, several groups have pioneered this field of investigation, suggesting that epigenetics could play an important role in the control of parasite gene expression. Histone modifications serve as an effective way to regulate gene transcription but they do not operate alone; rather, they act in concert with other putative epigenetic information carriers (histone variants, small RNAs) and DNA sequence-specific transcription factors to modulate the higher-order structure of the chromatin fibre and govern the on-time recruitment of the transcriptional machinery to specific genes. Regarding the 'histone code' hypothesis, the parasite is endowed with a rich repertoire of histone-modifying enzymes catalysing site-selective modifications, which are subsequently interpreted by effector proteins that recognize specific covalent marks. Still, several peculiarities seem unique to T. gondii. This review is a synthesis of the current knowledge of how epigenetics contribute to the control of gene expression in T. gondii and, likely, other Apicomplexa.

Chromatin modifications, epigenetics, and how protozoan parasites regulate their lives

“…Although the function of most of the predicted proteins has not been established, for many, the predicted function and specificity has been inferred bioinformatically [9, 10, 33]. The activity of the candidate modifying enzymes is predicted to induce changes in the chromatin structure and, therefore, could potentially affect the transcriptional profile of the organism.…”

“…Bioinformatic analysis of the T. gondii genome predicts epigenetic machinery that is similar to Plasmodium [10, 56], but characterization of the T. gondii epigenome has shown some surprising differences, which may reflect differences in biology or host range. In vivo, Toxoplasma responds to stress from the host by transitioning from the tachyzoite to a latent bradyzoite form.…”

“…While some of these SET proteins are orthologous to known histone modifying enzymes [10] or have PHD, chromo or bromo reader domains that suggest a nuclear function, most of these KMTs have not been functionally characterized. T. gondii protein methylases may have other roles beyond histone methylation and regulation of gene expression.…”

Canonical histone H2Ba and H2A.X dimerize in an opposite genomic localization to H2A.Z/H2B.Z dimers in Toxoplasma gondii

“…The parasites can also cause abortion or congenital birth defects if the mother becomes infected for the first time during pregnancy [7, 8]. Changes in gene expression are tightly controlled throughout the lytic and developmental cycles of T. gondii [9]. As in other species, a key contributor to gene expression regulation in T. gondii involves epigenetic control, including post-translational modifications (PTMs) of histones as well as histone variant replacement [10].…”

Transcript maturation in apicomplexan parasites

“…In parasite development there is a clear evidence of classical mechanisms based on cis-trans regulation of a core promoter complex, which involves the activity of large families of plant-related AP2 transcription factors [4–8] and chromatin remodelers [9, 10]. By contrast, the mechanisms responsible for cell cycle mRNA profiles in the asexual stages is less understood and here the role of ApiAP2 factors is much less clear.…”