title: Genome-wide identification of polycomb-associated RNAs by RIP-seq.
abstract: Polycomb proteins play essential roles in stem cell renewal and human disease. Recent studies of HOX genes and X inactivation have provided evidence for RNA cofactors in Polycomb repressive complex 2 (PRC2). Here we develop a RIP-seq method to capture the PRC2 transcriptome and identify a genome-wide pool of >9000 PRC2-interacting RNAs in embryonic stem cells. The transcriptome includes antisense, intergenic, and promoter-associated transcripts, as well as many unannotated RNAs. A large number of transcripts occur within imprinted regions, oncogene and tumor suppressor loci, and stem cell-related bivalent domains. We provide evidence for direct RNA-protein interactions, most likely via the Ezh2 subunit. We also identify Gtl2 RNA as a PRC2 cofactor that directs PRC2 to the reciprocally imprinted Dlk1 coding gene. Thus, Polycomb proteins interact with a genome-wide family of RNAs, some of which may be used as biomarkers and therapeutic targets for human disease.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Toshiro K
authors.initials: TK
authors.lastname: Ohsumi
authors.forename: Johnny T
authors.initials: JT
authors.lastname: Kung
authors.forename: Yuya
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Grau
authors.forename: Kavitha
authors.initials: K
authors.lastname: Sarma
authors.forename: Ji Joon
authors.initials: JJ
authors.lastname: Song
authors.forename: Robert E
authors.initials: RE
authors.lastname: Kingston
authors.forename: Mark
authors.initials: M
authors.lastname: Borowsky
authors.forename: Jeannie T
authors.initials: JT
authors.lastname: Lee
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000378:metabolism; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods*; D051379:Mice; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D011506:Proteins / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: C422882:MEG3 non-coding RNA, mouse; D063146:Polycomb-Group Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D012313:RNA