title: CAT7 and cat7l Long Non-coding RNAs Tune Polycomb Repressive Complex 1 Function during Human and Zebrafish Development.
abstract: The essential functions of polycomb repressive complex 1 (PRC1) in development and gene silencing are thought to involve long non-coding RNAs (lncRNAs), but few specific lncRNAs that guide PRC1 activity are known. We screened for lncRNAs, which co-precipitate with PRC1 from chromatin and found candidates that impact polycomb group protein (PcG)-regulated gene expression in vivo A novel lncRNA from this screen, CAT7, regulates expression and polycomb group binding at the MNX1 locus during early neuronal differentiation. CAT7 contains a unique tandem repeat domain that shares high sequence similarity to a non-syntenic zebrafish analog, cat7l Defects caused by interference of cat7l RNA during zebrafish embryogenesis were rescued by human CAT7 RNA, enhanced by interference of a PRC1 component, and suppressed by interference of a known PRC1 target gene, demonstrating cat7l genetically interacts with a PRC1. We propose a model whereby PRC1 acts in concert with specific lncRNAs and that CAT7/cat7l represents convergent lncRNAs that independently evolved to tune PRC1 repression at individual loci.
authors.affiliation: From the Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Mridula K
authors.initials: MK
authors.lastname: Ray
authors.affiliation: Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University and the Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts 02138.
authors.forename: Ole
authors.initials: O
authors.lastname: Wiskow
authors.affiliation: Center for Regenerative Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: King
authors.affiliation: Center for Regenerative Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Nidha
authors.initials: N
authors.lastname: Ismail
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Ayla
authors.initials: A
authors.lastname: Ergun
authors.affiliation: From the Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From the Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Plys
authors.affiliation: From the Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Davis
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Boston, Massachusetts, 02115, and.
authors.forename: Katie
authors.initials: K
authors.lastname: Kathrein
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Sadreyev
authors.affiliation: From the Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Borowsky
authors.affiliation: Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University and the Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts 02138, The Howard Hughes Medical Institute, Cambridge, MA 02138.
authors.forename: Kevin
authors.initials: K
authors.lastname: Eggan
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Boston, Massachusetts, 02115, and.
authors.forename: Leonard
authors.initials: L
authors.lastname: Zon
authors.affiliation: Center for Regenerative Medicine, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02114, jenna_galloway@hms.harvard.edu.
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Galloway
authors.affiliation: From the Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, kingston@molbio.mgh.harvard.edu.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Kingston
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D062085:RNA, Long Noncoding; D029961:Zebrafish Proteins; D063150:Polycomb Repressive Complex 1
keywords: CsCl density gradient; PRC1; chromatin; chromatin regulation; development; gene expression; long noncoding RNA (long ncRNA, lncRNA); mammal; polycomb; zebrafish