title: PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells.
abstract: EZH2 is the catalytic subunit of PRC2, a central epigenetic repressor essential for development processes in vivo and for the differentiation of embryonic stem cells (ESCs) in vitro. The biochemical function of PRC2 in depositing repressive H3K27me3 marks is well understood, but how it is regulated and directed to specific genes before and during differentiation remains unknown. Here, we report that PRC2 binds at low levels to a majority of promoters in mouse ESCs, including many that are active and devoid of H3K27me3. Using in vivo RNA-protein cross-linking, we show that EZH2 directly binds the 5' region of nascent RNAs transcribed from a subset of these promoters and that these binding events correlate with decreased H3K27me3. Our findings suggest a molecular mechanism by which PRC2 senses the transcriptional state of the cell and translates it into epigenetic information.
authors.affiliation: 1] Howard Hughes Medical Institute, New York University School of Medicine, New York, New York, USA. [2] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA.
authors.forename: Syuzo
authors.initials: S
authors.lastname: Kaneko
authors.forename: Jinsook
authors.initials: J
authors.lastname: Son
authors.forename: Steven S
authors.initials: SS
authors.lastname: Shen
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
authors.forename: Roberto
authors.initials: R
authors.lastname: Bonasio
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D051379:Mice; D008954:Models, Biological; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D063151:Polycomb Repressive Complex 2