| Autor: |
Vahid Asimi, Abhishek Sampath Kumar, Henri Niskanen, Christina Riemenschneider, Sara Hetzel, Julian Naderi, Nina Fasching, Niko Popitsch, Manyu Du, Helene Kretzmer, Zachary D. Smith, Raha Weigert, Maria Walther, Sainath Mamde, David Meierhofer, Lars Wittler, René Buschow, Bernd Timmermann, Ibrahim I. Cisse, Stefan L. Ameres, Alexander Meissner, Denes Hnisz |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Nature Genetics |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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