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

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...

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Bibliographic Details
Published in:Nature communications 2018-04, Vol.9 (1), p.1636-16, Article 1636
Main Authors: Ntini, Evgenia, Louloupi, Annita, Liz, Julia, Muino, Jose M., Marsico, Annalisa, Ørom, Ulf Andersson Vang
Format: Article
Language:English
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Chromatin
Datasets
Dkk1 protein
DNA methylation
Epigenetics
Gene expression
Gene loci
Gene regulation
Humanities and Social Sciences
multidisciplinary
Non-coding RNA
Nuclei
Post-transcription
Proteins
RNA polymerase
Science
Science (multidisciplinary)
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Summary: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. The functional role of dissociation of long ncRNAs from chromatin is poorly understood. Here, the authors provide evidence that release of the long ncRNA AROD from chromatin enhances DKK1 transcription, and suggest that this regulatory mechanism of transcription applies to a subset of long ncRNAs.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-04100-3