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  Hijacking of transcriptional condensates by endogenous retroviruses

Asimi, V., Sampath Kumar, A., Niskanen, H., Riemenschneider, C., Hetzel, S., Naderi, J., et al. (2022). Hijacking of transcriptional condensates by endogenous retroviruses. Nature Genetics, 54, 1238-1247. doi:10.1038/s41588-022-01132-w.

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NatureGenet_Asimi et al_2022.pdf (Publisher version), 28MB
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 Creators:
Asimi, Vahid1, Author           
Sampath Kumar, Abhishek2, Author           
Niskanen, Henri1, Author           
Riemenschneider, Christina2, Author           
Hetzel, Sara2, Author           
Naderi, Julian1, Author           
Fasching, Nina, Author
Popitsch, Niko , Author
Du, Manyu , Author
Kretzmer, Helene2, Author           
Smith, Zachary D. , Author
Weigert, Raha2, Author           
Walther, Maria2, Author           
Mamde, Sainath1, Author           
Meierhofer, David3, Author           
Wittler, Lars4, Author           
Buschow, Rene5, Author           
Timmermann, Bernd6, Author           
Cisse, Ibrahim I. , Author
Ameres, Stefan L. , Author
Meissner, Alexander2, Author           Hnisz, Denes1, Author            more..
Affiliations:
1Precision Gene Control (Denes Hnisz), Dept. of Genome Regulation, (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3014188              
2Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
3Mass Spectrometry Facility (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479669              
4Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              
5Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479668              
6Sequencing Core Facility (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

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 Abstract: 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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Language(s): eng - English
 Dates: 2022-05-262022-07-212022-08
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/s41588-022-01132-w
 Degree: -

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Title: Nature Genetics
  Other : Nature Genet.
Source Genre: Journal
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Publ. Info: New York, NY : Nature America, Inc.
Pages: 10 Volume / Issue: 54 Sequence Number: - Start / End Page: 1238 - 1247 Identifier: ISSN: 1061-4036 (print) 1546-1718 (online)
CoNE: https://pure.mpg.de/cone/journals/resource/954925598609