Hijacking of Transcriptional Condensates by Endogenous Retroviruses

Overview

Journal Nat Genet

Specialty Genetics

Date 2022 Jul 21

PMID 35864192

Authors

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

Rene Buschow

Bernd Timmermann

Ibrahim I Cisse

Stefan L Ameres

Alexander Meissner

Denes Hnisz

Affiliations

Soon will be listed here.

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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