Kinetoplastid-specific histone variant functions are conserved in Leishmania major

• Histone variants H2A.Z and H2B.V are essential in Leishmania major.
• Histone variant H3.V is not essential in L. major.
• H3.V loss does not affect read-through transcription, gene expression, viability nor virulence in a mouse model.
• Genetic tests suggest that the roles of epigenetic networks can be conserved (histone variants) or can diverge (DNA base J) during evolution.

Regions of transcription initiation and termination in kinetoplastid protists lack known eukaryotic promoter and terminator elements, although epigenetic marks such as histone variants and the modified DNA base J have been localized to these regions in Trypanosoma brucei, Trypanosoma cruzi, and/or Leishmania major. Phenotypes of base J mutants vary significantly across trypanosomatids, implying divergence in the epigenetic networks governing transcription during evolution. Here, we demonstrate that the histone variants H2A.Z and H2B.V are essential in L. major using a powerful quantitative plasmid segregation-based test. In contrast, H3.V is not essential for viability or normal growth in Leishmania. Steady-state transcript levels and the efficiency of transcription termination at convergent strand switch regions (SSRs) in H3V-null parasites were comparable to WT parasites. Our genetic tests show a conservation of histone variant phenotypes between L. major and T. brucei, unlike the diversity of phenotypes associated with genetic manipulation of the DNA base J modification.

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