Epigenetic landscape of the H3K27me3 mark in macrophages transformed by Theileria annulata.

Theileria annulata is an obligate intracellular parasite that induces bovine leukocyte transformation leading to uncontrolled proliferation and heightened dissemination of infected leukocytes. Early passage T. annulata-transformed macrophages are virulent, but with long-term culture, they become attenuated for dissemination. To investigate this phenotype from an epigenetic perspective, we focused on the important repressive histone marks, tri-methylated lysine 27 of histone H3 (H3K27me3) catalyzed by the Polycomb Repressive Complex 2. ChIP-seq revealed that the genomic distribution of H3K27me3 is heavily remodeled in attenuated macrophages, with many genes transitioning from a focal H3K27me3 peak around the transcription start site to larger chromatin domains. RNA-seq analysis following PRC2 inhibitor treatment reveals that fewer genes are derepressed in attenuated macrophages than in virulent macrophages, suggesting that broader H3K27me3 profiles do not systematically translate into increased gene silencing activity. Our findings shed light on the mechanisms underlying the dysregulation of epigenetic modifications in Theileria-induced leukocyte transformation.