Maintenance of spatial gene expression by Polycomb-mediated repression after formation of a vertebrate body plan

Polycomb group proteins are transcriptional repressors that are important regulators of cell fate during embryonic development. Among them, Ezh2 is responsible for catalyzing the epigenetic repressive mark H3K27me3 and is essential for animal development. The ability of zebrafish embryos lacking both maternal and zygotic ezh2 to form a normal body plan provides a unique model to comprehensively study Ezh2 function during early development in vertebrates. By using a multi-omics approach, we found that Ezh2 is required for the recruitment of H3K27me3 and Polycomb group protein Rnf2. However, in absence of Ezh2, only minor changes in global H3K4me3 levels and gene and protein expression occurred. These changes were mainly due to local deregulation of transcription factors outside their normal expression boundaries. Altogether, our results in zebrafish show that Polycomb-mediated gene repression is important only after the body plan is formed to maintain spatially restricted transcriptional profiles of Polycomb-targeted transcription factors.