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Long ncRNA A-ROD activates its target gene DKK1 at its release from chromatin

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  • Evgenia Ntini, Max Planck Institute for Molecular Genetics
  • ,
  • Annita Louloupi, Max Planck Institute for Molecular Genetics, School of Business and Economics
  • ,
  • Julia Liz, Max Planck Institute for Molecular Genetics
  • ,
  • Jose M. Muino, Humboldt-Universität zu Berlin
  • ,
  • Annalisa Marsico, Max Planck Institute for Molecular Genetics, School of Business and Economics
  • ,
  • Ulf Andersson Vang Ørom

Long ncRNAs are often enriched in the nucleus and at chromatin, but whether their dissociation from chromatin is important for their role in transcription regulation is unclear. Here, we group long ncRNAs using epigenetic marks, expression and strength of chromosomal interactions; we find that long ncRNAs transcribed from loci engaged in strong long-range chromosomal interactions are less abundant at chromatin, suggesting the release from chromatin as a crucial functional aspect of long ncRNAs in transcription regulation of their target genes. To gain mechanistic insight into this, we functionally validate the long ncRNA A-ROD, which enhances DKK1 transcription via its nascent spliced released form. Our data provide evidence that the regulatory interaction requires dissociation of A-ROD from chromatin, with target specificity ensured within the pre-established chromosomal proximity. We propose that the post-transcriptional release of a subset of long ncRNAs from the chromatin-associated template plays an important role in their function as transcription regulators.

Original languageEnglish
Article number1636
JournalNature Communications
Volume9
Number of pages16
ISSN2041-1723
DOIs
Publication statusPublished - 24 Apr 2018

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