The long non-coding RNA Paupar regulates the expression of both local and distal genes

Keith W Vance, Stephen N Sansom, Sheena Lee, Vladislava Chalei, Lesheng Kong, Sarah E Cooper, Peter L Oliver, Chris P Ponting

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Although some long noncoding RNAs (lncRNAs) have been shown to regulate gene expression in cis, it remains unclear whether lncRNAs can directly regulate transcription in trans by interacting with chromatin genome-wide independently of their sites of synthesis. Here, we describe the genomically local and more distal functions of Paupar, a vertebrate-conserved and central nervous system-expressed lncRNA transcribed from a locus upstream of the gene encoding the PAX6 transcription factor. Knockdown of Paupar disrupts the normal cell cycle profile of neuroblastoma cells and induces neural differentiation. Paupar acts in a transcript-dependent manner both locally, to regulate Pax6, as well as distally by binding and regulating genes on multiple chromosomes, in part through physical association with PAX6 protein. Paupar binding sites are enriched near promoters and can function as transcriptional regulatory elements whose activity is modulated by Paupar transcript levels. Our findings demonstrate that a lncRNA can function in trans at transcriptional regulatory elements distinct from its site of synthesis to control large-scale transcriptional programmes.

Original languageEnglish
Pages (from-to)296-311
Number of pages16
JournalThe EMBO Journal
Volume33
Issue number4
Early online date31 Jan 2014
DOIs
Publication statusPublished - 1 Feb 2014

Keywords

  • Animals
  • Binding Sites
  • Cell Line, Tumor
  • Chromatin
  • Conserved Sequence
  • Eye Proteins
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Genes, cdc
  • Genome-Wide Association Study
  • Homeodomain Proteins
  • Mice
  • Nerve Tissue Proteins
  • Neuroblastoma
  • Neurogenesis
  • Neurons
  • Paired Box Transcription Factors
  • Protein Binding
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Regulatory Elements, Transcriptional
  • Repressor Proteins
  • Transcription, Genetic
  • Transfection

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    Vance, K. W., Sansom, S. N., Lee, S., Chalei, V., Kong, L., Cooper, S. E., Oliver, P. L., & Ponting, C. P. (2014). The long non-coding RNA Paupar regulates the expression of both local and distal genes. The EMBO Journal, 33(4), 296-311. https://doi.org/10.1002/embj.201386225