The epigenetic landscape of kinetoplastid parasites: From histone post-translational modifications to emerging therapeutic strategies

Abstract

Kinetoplastids are parasites which cause various neglected tropical diseases. A hallmark feature of their genomic composition is the presence of polycistronic transcription, a phenomenon that involves the transcription of multiple genes into a single mRNA molecule, along with unconventional modes of gene regulation. In these organisms, histone variants and post-translational modifications play pivotal roles in modulating chromatin structure and transcriptional activity. This review provides a comprehensive overview of histone variants and post-translational modifications identified across Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei, detailing both the diversity of modifications and their known functional roles. This review also focuses on the writers, erasers, and readers proteins, including available three-dimensional structural data, to better understand their contribution to chromatin regulation, cell cycle progression, and parasite adaptation. Concurrently, this review offers a synopsis of therapeutic endeavors that have targeted these pathways, emphasizing the outcomes of in silico, in vitro and in vivo studies. This comprehensive review underscores the potential of unraveling kinetoplastid epigenetic mechanisms as a promising avenue for developing innovative treatments against these major human pathogens.

Keywords: Antikinetoplastid; Bromodomain; Epigenetics; Histone modifiers; Histone post-translational modifications; Inhibitors.