The study investigates the roles of Polycomb group (PcG) proteins in cell fate transitions by genome-wide mapping of their target genes in human embryonic fibroblasts. Using chromatin immunoprecipitation (ChIP) and tiled arrays, the researchers identified over 1000 genes co-occupied by PcG complexes, including Polycomb-Repressive Complex 1 (PRC1), PRC2, and tri-methylated histone H3K27. These genes are strongly biased towards embryonic development and cell fate decisions. The study found that PcGs are involved in the regulation of both stem cell- and differentiation-specific genes. In neuronal differentiation, PcGs are displaced from genes activated during differentiation, while they remain bound to genes repressed during differentiation. The results suggest that PcGs form part of a preprogrammed memory system established during embryogenesis, marking key genes for repressive signals in subsequent developmental and differentiation processes. The findings provide insights into the mechanisms by which PcGs control cell fate decisions and their potential roles in cancer.The study investigates the roles of Polycomb group (PcG) proteins in cell fate transitions by genome-wide mapping of their target genes in human embryonic fibroblasts. Using chromatin immunoprecipitation (ChIP) and tiled arrays, the researchers identified over 1000 genes co-occupied by PcG complexes, including Polycomb-Repressive Complex 1 (PRC1), PRC2, and tri-methylated histone H3K27. These genes are strongly biased towards embryonic development and cell fate decisions. The study found that PcGs are involved in the regulation of both stem cell- and differentiation-specific genes. In neuronal differentiation, PcGs are displaced from genes activated during differentiation, while they remain bound to genes repressed during differentiation. The results suggest that PcGs form part of a preprogrammed memory system established during embryogenesis, marking key genes for repressive signals in subsequent developmental and differentiation processes. The findings provide insights into the mechanisms by which PcGs control cell fate decisions and their potential roles in cancer.