Protein posttranslational modifications of Giardia histones

ABSTRACT: Diarrheal disease caused by Giardia duodenalis is highly prevalent, totalling over 200 million cases globally each year. The processes which drive parasite virulence, host immune evasion and transmission involve coordinated gene expression, which are likely post-transcriptionally regulated. Epigenetic regulatory systems are eukaryote-conserved, including in deep-branching excavates such as Giardia, with several studies already implicating histone post-translational modifications (PTMs) in regulation of its pathogenesis and life cycle. However, further insights into Giardia chromatin dynamics have been hindered by a lack of site-specific data. Using mass spectrometry, we have provided the first molecular map of histone methylation, acetylation and phosphorylation modifications in Giardia core histones. We have identified over 50 previously unreported histone modifications, including recognised epigenetic sites, combinatorial modifications indicative of PTM crosstalk, and co-occurring modifications previously correlated in model eukaryotes. These demonstrate a conserved histone code in Giardia that is equivalent to many other eukaryotes, and suggest that similar epigenetic mechanisms are in place in this parasite. Further, we used sequence, domain and structural homology to annotate putative histone enzyme networks in Giardia, highlighting representative chromatin modifiers which appear sufficient for identified sites, particularly those from H3 and H4 variants. This study is the first and most comprehensive, complete and accurate view of Giardia histone PTMs to date, and a substantial step towards understanding their associations in parasite development and virulence.

INSTRUMENT(S):

ORGANISM(S): Giardia Intestinalis Assemblage A

TISSUE(S): Trophozoite, Binucleate

DISEASE(S): Giardiasis

SUBMITTER: Samantha Emery  

LAB HEAD: A/Prof Aaron R. Jex

PROVIDER: PXD019949 | Pride | 2025-08-28

REPOSITORIES: Pride