Polycomb group (PcG) proteins are transcriptional repressors, which regulate 
proliferation and cell fate decisions during development, and their deregulated 
expression is a frequent event in human tumours. The Polycomb repressive complex 
2 (PRC2) catalyzes trimethylation (me3) of histone H3 lysine 27 (K27), and it is 
believed that this activity mediates transcriptional repression. Despite the 
recent progress in understanding PcG function, the molecular mechanisms by which 
the PcG proteins repress transcription, as well as the mechanisms that lead to 
the activation of PcG target genes are poorly understood. To gain insight into 
these mechanisms, we have determined the global changes in histone modifications 
in embryonic stem (ES) cells lacking the PcG protein Suz12 that is essential for 
PRC2 activity. We show that loss of PRC2 activity results in a global increase 
in H3K27 acetylation. The methylation to acetylation switch correlates with the 
transcriptional activation of PcG target genes, both during ES cell 
differentiation and in MLL-AF9-transduced hematopoietic stem cells. Moreover, we 
provide evidence that the acetylation of H3K27 is catalyzed by the 
acetyltransferases p300 and CBP. Based on these data, we propose that the PcG 
proteins in part repress transcription by preventing the binding of 
acetyltransferases to PcG target genes.