Epigenetic Reprogramming of Host Chromatin by the Transforming Parasite Theileria annulata

Theileria annulata, a transforming apicomplexan parasite, extensively reprograms the chromatin architecture of bovine leukocytes to facilitate infection and cellular transformation. To elucidate the underlying epigenetic mechanisms, we characterized the chromatin landscape of infected lymphocytes using integrated proteomic, imaging, and functional assays. Our findings reveal that T. annulata lacks the DNA damage marker {gamma}H2A.X and its associated SQ/TQ motif, indicating an evolutionary divergence from canonical DNA repair signalling pathways. High-resolution profiling of histone post-translational modifications (PTMs) demonstrated distinct nuclear compartmentalization, with host (H3K27me3, H3K9me1/2), parasite-predominant modifications (H3K4me3, H3K18me1, H3K27ac, H3K9ac, and H3K36me3), and shared modifications (e.g., H3K4me1/2, H3K36me2, H4K5/8/12/16ac, H3K9me3 and H4K91Ac) suggesting a coordinated epigenetic strategy driving host cell programs to sustain proliferation and survival. Our study delineates a novel host-parasite epigenetic interface, positioning T. annulata as a unique model of epigenetic parasitism. By bridging parasitology and cancer epigenetics, these findings unveil new therapeutic opportunities targeting chromatin vulnerabilities in parasite-induced transformation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/684985v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1bd0e05org.highwire.dtl.DTLVardef@e37ea4org.highwire.dtl.DTLVardef@18f78d5org.highwire.dtl.DTLVardef@460eb4_HPS_FORMAT_FIGEXP M_FIG C_FIG