Transcriptomics

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Hijacking of transcriptional condensates by endogenous retroviruses


ABSTRACT: Most endogenous retroviruses (ERVs) in mammals are incapable of retrotransposition; therefore, why ERV de-repression is associated with lethality during early development has been a mystery. Here we report that rapid and selective degradation of the TRIM28 heterochromatin adapter protein triggers dissociation of transcriptional condensates from loci encoding super-enhancer -driven pluripotency genes, and their association with transcribed ERV loci in murine embryonic stem cells. Knockdown of ERV RNAs or forced expression of super-enhancer -enriched transcription factors rescued condensate localization at super-enhancers in TRIM28-degraded cells. In a biochemical reconstitution system, ERV RNA facilitated partitioning of RNA Polymerase II, and the Mediator co- activator 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 non-coding nascent RNAs, including those produced by retrotransposons, may facilitate “hijacking” of transcriptional condensates in various developmental and disease contexts.

ORGANISM(S): Mus musculus

PROVIDER: GSE159468 | GEO | 2022/03/30

REPOSITORIES: GEO

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