title: A strand-specific switch in noncoding transcription switches the function of a Polycomb/Trithorax response element.
abstract: Polycomb/Trithorax response elements (PRE/TREs) can switch their function reversibly between silencing and activation by mechanisms that are poorly understood. Here we show that a switch in forward and reverse noncoding transcription from the Drosophila melanogaster vestigial (vg) PRE/TRE switches the status of the element between silencing (induced by the forward strand) and activation (induced by the reverse strand). In vitro, both noncoding RNAs inhibit PRC2 histone methyltransferase activity, but, in vivo, only the reverse strand binds PRC2. Overexpression of the reverse strand evicts PRC2 from chromatin and inhibits its enzymatic activity. We propose that the interaction of RNAs with PRC2 is differentially regulated in vivo, allowing regulated inhibition of local PRC2 activity. Genome-wide analysis shows that strand switching of noncoding RNAs occurs at several hundred Polycomb-binding sites in fly and vertebrate genomes. This work identifies a previously unreported and potentially widespread class of PRE/TREs that switch function by switching the direction of noncoding RNA transcription.
authors.affiliation: IMBA, Institute of Molecular Biotechnology GmBH, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Veronika A
authors.initials: VA
authors.lastname: Herzog
authors.affiliation: IMBA, Institute of Molecular Biotechnology GmBH, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.|Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
authors.forename: Adelheid
authors.initials: A
authors.lastname: Lempradl
authors.affiliation: IMBA, Institute of Molecular Biotechnology GmBH, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Johanna
authors.initials: J
authors.lastname: Trupke
authors.affiliation: IMBA, Institute of Molecular Biotechnology GmBH, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Helena
authors.initials: H
authors.lastname: Okulski
authors.affiliation: IMBA, Institute of Molecular Biotechnology GmBH, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Altmutter
authors.affiliation: IMBA, Institute of Molecular Biotechnology GmBH, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: Ruge
authors.affiliation: CeMM, Research Center for Molecular Medicine, Lazarettgasse 14, 1090 Vienna, Austria.
authors.forename: Bernd
authors.initials: B
authors.lastname: Boidol
authors.affiliation: CeMM, Research Center for Molecular Medicine, Lazarettgasse 14, 1090 Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kubicek
authors.affiliation: IMP, Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Schmauss
authors.affiliation: IMP, Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Aumayr
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Ruf
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pospisilik
authors.affiliation: IMBA, Institute of Molecular Biotechnology GmBH, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.|The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dimond
authors.affiliation: IMBA, Institute of Molecular Biotechnology GmBH, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Hasene Basak
authors.initials: HB
authors.lastname: Senergin
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota. Minneapolis, Minnesota, USA.
authors.forename: Marcus L
authors.initials: ML
authors.lastname: Vargas
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota. Minneapolis, Minnesota, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Simon
authors.affiliation: IMBA, Institute of Molecular Biotechnology GmBH, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Leonie
authors.initials: L
authors.lastname: Ringrose
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002843:Chromatin / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster; D005812:Genes, Switch; D049750:Genome, Insect; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D008969:Molecular Sequence Data; D063146:Polycomb-Group Proteins / Q000235:genetics*; D022661:RNA, Untranslated; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D063146:Polycomb-Group Proteins; D022661:RNA, Untranslated; D014157:Transcription Factors; C512571:trx protein, Drosophila; D011495:Histone-Lysine N-Methyltransferase; C524066:PRC2 protein, Drosophila
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