Toxoplasma evolved two ISWI proteins: TgSNF2h and TgSNF2L. Despite looking similar structurally, these two have very different roles. TgSNF2h forms an ISWI complex with the transcription factor AP2VIII-2 and the scaffold protein TgRFTS. Spoiler: TgSNF2L will step soon into the spotlight.

We used auxin-inducible degradation to knock down TgSNF2h and TgRFTS. The result? Massive changes in chromatin structure and gene expression. Chromatin closed. Parasite development stalled.

And here's the twist: MORC binding drops when TgSNF2h is gone. The ISWI complex (via TgSNF2h) acts as a gatekeeper, deciding what genes stay on or off at each stage of the parasite’s life. In short: ISWI controls parasite identity.

We think the ISWI–MORC duo might replace classical insulators like CTCF, which are missing in Apicomplexa—hinting at a novel looping mechanism. Opens new doors into chromatin architecture in early-diverging eukaryotes!

Big thanks to Matthew Bowler and Yohann Couté for their constant support! Huge shoutout to BelenPachano – a rockstar PhD student. Cheers to Christopher Swale for co-directing this project, and to all the authors who made this great project happen!