Polycomb-group proteins are transcriptional repressors with essential roles in 
embryonic development. Polycomb repressive complex 2 (PRC2) contains the 
methyltransferase activity for Lys27. However, the role of other histone 
modifications in regulating PRC2 activity is just beginning to be understood. 
Here we show that direct recognition of methylated histone H3 Lys36 (H3K36me), a 
mark associated with activation, by the PRC2 subunit Phf19 is required for the 
full enzymatic activity of the PRC2 complex. Using NMR spectroscopy, we provide 
structural evidence for this interaction. Furthermore, we show that Phf19 binds 
to a subset of PRC2 targets in mouse embryonic stem cells and that this is 
required for their repression and for H3K27me3 deposition. These findings show 
that the interaction of Phf19 with H3K36me2 and H3K36me3 is essential for PRC2 
complex activity and for proper regulation of gene repression in embryonic stem 
cells.