Elucidating the role of PRC1 in epigenetic switches and cell fate commitment

Tissue development involves dynamic changes in both the epigenetic landscapes of DNA regulatory elements and in chromatin accessibility; together, these changes instruct lineage-specific transcription factors to execute precise transcriptional programs and establish new cellular identities. However, little is known about how epigenetic mechanisms are fine-tuned in response to spatiotemporal signals that converge on chromatin during development. Here, we study the role of Polycomb repressive complex 1 (PRC1) – an evolutionarily conserved epigenetic regulator of cellular identity, utilizing the embryonic murine skin as a paradigm for tissue development. Epigenetic profiling of the PRC1 epigenetic landscape in basal layer epidermal stem cells uncovered that, despite well-established repressor functions, PRC1 binds to both active and repressed genes. Deletion of PRC1 activity in epidermal stem cells resulted in massive upregulation of its repressed target genes, and a subtle downregulation in the expression of a subset of its active targets. PRC1 gain-of-function resulted in increased binding of PRC1 subunits to active genes and an upregulation in their expression, indicating that PRC1 plays dual roles in transcription regulation by on one hand repressing the expression of non-epidermal genes, while on the other hand promoting the expression of epidermal lineage genes. Transcriptional analysis at earlier developmental stages uncovered that the expression of PRC1 target genes is dynamic and rapidly changes during epidermal commitment, suggesting a role for PRC1 in epigenetic switches – a transition between transcriptional active to repressed state, and vice versa, thereby enabling to turn ON and OFF transcriptional programs and establish new cellular identities.