Temporal depletion of PRC2 reveals multi-layered controls of cell fate decisions [CUT&Tag II]

ABSTRACT: The repression of developmental genes by Polycomb repressive complex 2 (PRC2) is well documented, however constitutive deletion studies provide only limited insights of how deregulation is linked to developmental lethality. Here, we overcome this by using a protein degradation strategy combined with a scalable embryoid model. With the temporal and acute PRC2 loss we fine-mapped developmental failures, which shows that in addition to the canonical posterior phenotypes, PRC2-depleted embryoids display unexpected ectopic expression of anterior and lateral lineage genes. We find the enrichment of H3K27me3 generally predicts lineage sensitivity, but only when combined with the presence of lineage-specific transcription factors, explaining which genes are activated upon PRC2 loss. Our integrative expression and chromatin profiling highlights that in contrast to the developmental genes, pluripotent genes fail to silence with early onset of PRC2 depletion but are not affected after a few days of differentiation. Together, our results shed new light on the developmental requirements for PRC2-mediated repression at temporal, tissue, and gene-specific resolutions.

ORGANISM(S): Mus musculus

PROVIDER: GSE346324 | GEO | 2026/10/16

REPOSITORIES: GEO