Ezh2 Control of Bivalent Genes Fine-Tunes Developmental Competence During Retinogenesis

Here, we characterize the genomic distribution of EZH2, the catalytic subunit of the Polycomb repressive complex 2 (PRC2), and examine its relationship to chromatin state and gene expression in the developing mouse retina.

EZH2 is enriched at promoters and regulatory regions marked by H3K27me3, consistent with its role in transcriptional repression. Integrated analysis of EZH2 binding, H3K27me3 deposition, and transcriptomic changes upon Ezh2 loss revealed that bivalent genes marked by Ezh2 are particularly susceptible to derepression, highlighting a poised yet transcriptionally restrained state maintained by EZH2 in RPCs. We provide evidence for coordinated activity between retinal progenitor cell transcription factors and PRC2 in fine-tuning developmental gene-expression programs and controlling retinal cell-fate decisions.