Abstract
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.
Highlights
Histone posttranslational modifications (PTMs) modulate several eukaryotic cellular processes, including transcription, replication, and repair
Kawahara et al [40] found that T. brucei HAT1 (TbHAT1) depletion resulted in the cells entering mitosis without undergoing nuclear DNA replication. Considering this with the fact that several trypanosomatid origins overlap with transcription start regions that are enriched in acetyl-H2A.Z, one might speculate that H2A.Z acetylation is critical for origin activation
While studies of Trypanosoma are forging ahead, information regarding the global landscape of histone PTMs in Leishmania would give a fresh impetus to studies in these organisms as well
Summary
The organization of eukaryotic DNA into chromatin renders it compact enough to fit into the nucleus, simultaneously protecting it from damage. LANDSCAPE OF HISTONE MODIFICATIONS IN TRYPANOSOMATIDS The early diverging trypanosomatids possess all four canonical core histones as well as four variant histones, H2A.Z, H2.V, H3.V, and H4.V, H4.V has been identified only in T. brucei so far As their histones are divergent from those of conventional eukaryotes (they share 40 to 60% identity with the core histones of higher eukaryotes S. cerevisiae, S. pombe, Drosophila melanogaster, Caenorhabditis elegans, Mus musculus, and Homo sapiens), as well as those of early diverging eukaryotes of other groups (sharing 35 to 60% identity with the core histones of Plasmodium falciparum, Toxoplasma gondii, Cryptosporidium parvum, and Trichomonas vaginalis), the repertoire of PTMs they carry vary. Over ϳ170 PTMs were identified in the tails and globular domains of the canonical and variant histones of T. cruzi These included 13 distinct types of PTMs, eight of which were detected in trypanosomatids for the first time.
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