title: Interactions with RNA direct the Polycomb group protein SCML2 to chromatin where it represses target genes.
abstract: Polycomb repressive complex-1 (PRC1) is essential for the epigenetic regulation of gene expression. SCML2 is a mammalian homolog of Drosophila SCM, a Polycomb-group protein that associates with PRC1. In this study, we show that SCML2A, an SCML2 isoform tightly associated to chromatin, contributes to PRC1 localization and also directly enforces repression of certain Polycomb target genes. SCML2A binds to PRC1 via its SPM domain and interacts with ncRNAs through a novel RNA-binding region (RBR). Targeting of SCML2A to chromatin involves the coordinated action of the MBT domains, RNA binding, and interaction with PRC1 through the SPM domain. Deletion of the RBR reduces the occupancy of SCML2A at target genes and overexpression of a mutant SCML2A lacking the RBR causes defects in PRC1 recruitment. These observations point to a role for ncRNAs in regulating SCML2 function and suggest that SCML2 participates in the epigenetic control of transcription directly and in cooperation with PRC1.DOI: http://dx.doi.org/10.7554/eLife.02637.001.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Howard Hughes Medical Institute, New York University School of Medicine, New York, United States.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bonasio
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Howard Hughes Medical Institute, New York University School of Medicine, New York, United States.
authors.forename: Emilio
authors.initials: E
authors.lastname: Lecona
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Howard Hughes Medical Institute, New York University School of Medicine, New York, United States.
authors.forename: Varun
authors.initials: V
authors.lastname: Narendra
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Howard Hughes Medical Institute, New York University School of Medicine, New York, United States.
authors.forename: Philipp
authors.initials: P
authors.lastname: Voigt
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, United States Yale Cancer Center, Yale University School of Medicine, New Haven, United States.
authors.forename: Fabio
authors.initials: F
authors.lastname: Parisi
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, United States Yale Cancer Center, Yale University School of Medicine, New Haven, United States.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Kluger
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Howard Hughes Medical Institute, New York University School of Medicine, New York, United States danny.reinberg@nyumc.org.
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012313:RNA / Q000378:metabolism*; D022661:RNA, Untranslated / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic
chemical_list: C069077:BMI1 protein, human; D002843:Chromatin; D063146:Polycomb-Group Proteins; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C119751:SCML2 protein, human; D012313:RNA; D063150:Polycomb Repressive Complex 1
keywords: MBT; PRC1; Polycomb; SCML2; chromatin; noncoding RNAs