"Temporal PRC2 depletion uncovers regulatory principles of cell fate decisions"

Contact: maud.borensztein@igmm.cnrs.fr

IGMM External Seminar

Abstract:

The repression of genes by Polycomb repressive complex 2 (PRC2) is well documented and constitutive deletion studies have highlighted its essential role in development. However, exactly how loss of the complex is linked to these phenotypes remains incompletely understood and difficult to study in vivo. Here, we applied a rapid protein degradation strategy combined with a scalable embryoid model to trigger temporal PRC2 loss. This allowed us to fine-map developmental failures and showed that in addition to the canonical posterior phenotypes, PRC2-depleted embryoids also display ectopic expression of anterior and lateral lineage genes. Moreover, we find that lineages show distinct responses to PRC2 loss, which is likely associated with the activity of their specific transcription factors. Our integrative expression and chromatin profiling highlights that in contrast to developmental genes, pluripotency- associated genes only fail to silence with early PRC2 depletion but are unaffected once cells exited pluripotency. Together, our results expand our current understanding of PRC2-mediated repression with increased temporal and lineage resolution.