A Polycomb repressive complex is required for RNAi-mediated heterochromatin formation and dynamic distribution of nuclear bodies

Polycomb group (PcG) proteins are widely utilized for transcriptional repression in eukaryotes. Here, we characterize, in the protist Tetrahymena thermophila, the EZL1 (E(z)-like 1) complex, with components conserved in metazoan Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2). The EZL1 complex is required for histone H3 K27 and K9 methylation, heterochromatin formation, transposable element control, and programmed genome rearrangement. The EZL1 complex interacts with EMA1, a helicase required for RNA interference (RNAi). This interaction is implicated in co-transcriptional recruitment of the EZL1 complex. Binding of H3K27 and H3K9 methylation by PDD1-another PcG protein interacting with the EZL1 complex-reinforces its chromatin association. The EZL1 complex is an integral part of Polycomb bodies, which exhibit dynamic distribution in Tetrahymena development: Their dispersion is driven by chromatin association, while their coalescence by PDD1, likely via phase separation. Our results provide a molecular mechanism connecting RNAi and Polycomb repression, which coordinately regulate nuclear bodies and reorganize the genome.

Automated summary

In this study, the EZL1 complex in the protist Tetrahymena thermophila was characterized, revealing its essential role in histone methylation, heterochromatin formation, and genome rearrangement. The interaction between the EZL1 complex and EMA1, as well as PDD1, reinforces its chromatin association and contributes to the dynamic distribution of Polycomb bodies in Tetrahymena development. These findings provide a molecular mechanism linking RNAi and Polycomb repression, ultimately regulating nuclear bodies and genome organization.