EnP1 exploits H2Aub-dependent epigenetic reprogramming to promote microsporidia proliferation in host cells

Microsporidia, as opportunistic parasitic pathogens, constitute a formidable threat to human health. Although the regulatory circuitry of the nucleus-targeted effector EnP1 is highly intricate and remains only partially elucidated, our investigation has revealed histone H2A as an additional binding partner of EnP1 and demonstrated that both EnP1 overexpression and microsporidia infection precipitate the monoubiquitination of H2A (H2Aub) via the downregulation of BAP1 expression. Subsequent analyses disclosed that augmented H2Aub levels significantly promote microsporidia proliferation, while diminished H2Aub levels exert an inhibitory effect on pathogen expansion. Moreover, EnP1 enhances the recruitment of H2Aub to the promoter region of SLC7A11, thereby upregulating its expression. Collectively, these findings underscore that EnP1 modulates the ferroptotic state of host cells through H2Aubmediated epigenetic reprogramming, ultimately facilitating pathogen propagation. This study endeavors to elucidate the critical survival strategies of microsporidia within host cells mediated by EnP1 and to unravel the multifaceted interplay between these pathogens and their hosts. The raw experimental data, including immunoblotting results and statistical analyses, are contained in PDF/Excel files named according to their corresponding figure order.