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dc.contributor.authorAmaral, Paulo
dc.contributor.authorLeonardi, Tommaso
dc.contributor.authorHan, Namshik
dc.contributor.authorViré, Emmanuelle
dc.contributor.authorGascoigne, Dennis
dc.contributor.authorArias-Carrasco, Raúl
dc.contributor.authorBüscher, Magdalena
dc.contributor.authorZhang, Anda
dc.contributor.authorPluchino, Stefano
dc.contributor.authorMaracaja-Coutinho, Vinicius
dc.contributor.authorNakaya, Helder
dc.contributor.authorHemberg, Martin
dc.contributor.authorShiekhattar, Ramin
dc.contributor.authorEnright, Anton
dc.contributor.authorKouzarides, Tony
dc.description.abstractThe mammalian genome is transcribed into large numbers of long noncoding RNAs (lncRNAs), but the definition of functional lncRNA groups has proven difficult, partly due to their low sequence conservation and lack of identified shared properties. Here we consider positional conservation across mammalian genomes as an indicator of functional commonality. We identify 665 conserved lncRNA promoters in mouse and human genomes that are preserved in genomic position relative to orthologous coding genes. The identified ‘positionally conserved’ lncRNA genes are primarily associated with developmental transcription factor loci with which they are co-expressed in a tissue-specific manner. Strikingly, over half of all positionally conserved RNAs in this set are linked to distinct chromatin organization structures, overlapping the binding sites for the CTCF chromatin organizer and located at chromatin loop anchor points and borders of topologically associating domains (TADs). These t opological a nchor p oint (tap)RNAs possess conserved sequence domains that are enriched in potential recognition motifs for Zinc Finger proteins. Characterization of these noncoding RNAs and their associated coding genes shows that they are functionally connected: they regulate each other’s expression and influence the metastatic phenotype of cancer cells in vitro in a similar fashion. Thus, interrogation of positionally conserved lncRNAs identifies a new subset of tapRNAs with shared functional properties. These results provide a large dataset of lncRNAs that conform to the “extended gene” model, in which conserved developmental genes are genomically and functionally linked to regulatory lncRNA loci across mammalian evolution.
dc.publisherSpringer Nature
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.titleGenomic positional conservation identifies topological anchor point (tap)RNAs linked to developmental loci
prism.publicationNameGenome Biology
dc.contributor.orcidDe Paiva Rosa Amaral, Paulo [0000-0002-6696-5142]
dc.contributor.orcidPluchino, Stefano [0000-0002-6267-9472]
dc.contributor.orcidEnright, Anton [0000-0002-6090-3100]
dc.contributor.orcidKouzarides, Tony [0000-0002-8918-4162]
rioxxterms.typeJournal Article/Review

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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)