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Hijacking of transcriptional condensates by endogenous retroviruses.
Asimi, Vahid; Sampath Kumar, Abhishek; Niskanen, Henri; Riemenschneider, Christina; Hetzel, Sara; Naderi, Julian; Fasching, Nina; Popitsch, Niko; Du, Manyu; Kretzmer, Helene; Smith, Zachary D; Weigert, Raha; Walther, Maria; Mamde, Sainath; Meierhofer, David; Wittler, Lars; Buschow, René; Timmermann, Bernd; Cisse, Ibrahim I; Ameres, Stefan L; Meissner, Alexander; Hnisz, Denes.
Afiliación
  • Asimi V; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Sampath Kumar A; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
  • Niskanen H; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Riemenschneider C; Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
  • Hetzel S; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Naderi J; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Fasching N; Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
  • Popitsch N; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Du M; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Kretzmer H; Institute of Molecular Biotechnology (IMBA), Vienna BioCenter (VBC), Vienna, Austria.
  • Smith ZD; Institute of Molecular Biotechnology (IMBA), Vienna BioCenter (VBC), Vienna, Austria.
  • Weigert R; Department of Biochemistry and Cell Biology, Max Perutz Labs, University of Vienna, Vienna BioCenter (VBC), Vienna, Austria.
  • Walther M; Department of Physics, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Mamde S; Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
  • Meierhofer D; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Wittler L; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Buschow R; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
  • Timmermann B; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Cisse II; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Ameres SL; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Meissner A; Max Planck Institute for Molecular Genetics, Mass Spectrometry Facility, Berlin, Germany.
  • Hnisz D; Department of Developmental Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Nat Genet ; 54(8): 1238-1247, 2022 08.
Article en En | MEDLINE | ID: mdl-35864192
Most endogenous retroviruses (ERVs) in mammals are incapable of retrotransposition; therefore, why ERV derepression is associated with lethality during early development has been a mystery. Here, we report that rapid and selective degradation of the heterochromatin adapter protein TRIM28 triggers dissociation of transcriptional condensates from loci encoding super-enhancer (SE)-driven pluripotency genes and their association with transcribed ERV loci in murine embryonic stem cells. Knockdown of ERV RNAs or forced expression of SE-enriched transcription factors rescued condensate localization at SEs in TRIM28-degraded cells. In a biochemical reconstitution system, ERV RNA facilitated partitioning of RNA polymerase II and the Mediator coactivator into phase-separated droplets. In TRIM28 knockout mouse embryos, single-cell RNA-seq analysis revealed specific depletion of pluripotent lineages. We propose that coding and noncoding nascent RNAs, including those produced by retrotransposons, may facilitate 'hijacking' of transcriptional condensates in various developmental and disease contexts.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retrovirus Endógenos Límite: Animals Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retrovirus Endógenos Límite: Animals Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos