4DCellFate

Developing a global understanding of the PRC and NuRD complexes in stem cell differentiation and in disease

Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity — Di Croce and collaborator labs (2012)

Nature Structural & Molecular Biology

Cecilia Ballaré, Martin Lange, Audrone Lapinaite, Gloria Mas Martin, Lluis Morey, Gloria Pascual, Robert Liefke, Bernd Simon, Yang Shi, Or Gozani, Teresa Carlomagno, Salvador Aznar Benitah & Luciano Di Croce 

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. 

Nat Struct Mol Biol. 2012 Dec;19(12):1257-65. doi: 10.1038/nsmb.2434

Attached media: 
AttachmentSize
PDF icon nsmb.2434.pdf1.49 MB