Comprehensive multi-omics analysis uncovers a group of TGF-β-regulated genes among lncRNA EPR direct transcriptional targets

Ettore Zapparoli, Paola Briata, Martina Rossi, Lorenzo Brondolo, Gabriele Bucci, Roberto Gherzi

Research output: Contribution to journalArticlepeer-review

Abstract

Long non-coding RNAs (lncRNAs) can affect multiple layers of gene expression to control crucial cellular functions. We have previously demonstrated that the lncRNA EPR, by controlling gene expression at different levels, affects cell proliferation and migration in cultured mammary gland cells and impairs breast tumor formation in an orthotopic transplant model in mice. Here, we used ChIRP-Seq to identify EPR binding sites on chromatin of NMuMG mammary gland cells overexpressing EPR and identified its trans binding sites in the genome. Then, with the purpose of relating EPR/chromatin interactions to the reshaping of the epitranscriptome landscape, we profiled histone activation marks at promoter/enhancer regions by ChIP-Seq. Finally, we integrated data derived from ChIRP-Seq, ChIP-Seq as well as RNA-Seq in a comprehensive analysis and we selected a group of bona fide direct transcriptional targets of EPR. Among them, we identified a subset of EPR targets whose expression is controlled by TGF-β with one of them-Arrdc3-being able to modulate Epithelial to Mesenchymal Transition. This experimental framework allowed us to correlate lncRNA/chromatin interactions with the real outcome of gene expression and to start defining the gene network regulated by EPR as a component of the TGF-β pathway.

Original languageEnglish
Pages (from-to)9053-9066
Number of pages14
JournalNucleic Acids Research
Volume48
Issue number16
DOIs
Publication statusPublished - Sep 18 2020

ASJC Scopus subject areas

  • Genetics

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