Histone Modifications and Other Facets of Epigenetic Regulation in Trypanosomatids: Leaving Their Mark.

Histone posttranslational modifications (PTMs) modulate several eukaryotic cellular processes, including transcription, replication, and repair. Vast arrays of modifications have been identified in conventional eukaryotes over the last 20 to 25 years. While initial studies uncovered these primarily on histone tails, multiple modifications were subsequently found on the central globular domains as well. Histones are evolutionarily conserved across eukaryotes, and a large number of their PTMs and the functional relevance of these PTMs are largely conserved. Trypanosomatids, however, are early diverging eukaryotes. Although possessing all four canonical histones as well as several variants, their sequences diverge from those of other eukaryotes, particularly in the tails. Consequently, the modifications they carry also vary. Initial analyses almost 15 years ago suggested that trypanosomatids possessed a smaller collection of histone modifications. However, exhaustive high resolution mass spectrometry analyses in the last few years have overturned this belief, and it is now evident that the "histone code" proposed by Allis and coworkers in the early years of this century is as complex in these organisms as in other eukaryotes. Trypanosomatids cause several diseases, and the members of this group of organisms have varied lifestyles, evolving diverse mechanisms to evade the host immune system, some of which have been found to be principally controlled by epigenetic mechanisms. This minireview aims to acquaint the reader with the impact of histone PTMs on trypanosomatid cellular processes, as well as other facets of trypanosomatid epigenetic regulation, including the influence of three-dimensional (3D) genome architecture, and discusses avenues for future investigations.