The long non-coding RNA Dali is an epigenetic regulator of neural differentiation

Vladislava Chalei, Stephen N Sansom, Lesheng Kong, Sheena Lee, Juan F Montiel, Keith W Vance, Chris P Ponting

Research output: Contribution to journalArticlepeer-review

Abstract

Many intergenic long noncoding RNA (lncRNA) loci regulate the expression of adjacent protein coding genes. Less clear is whether intergenic lncRNAs commonly regulate transcription by modulating chromatin at genomically distant loci. Here, we report both genomically local and distal RNA-dependent roles of Dali, a conserved central nervous system expressed intergenic lncRNA. Dali is transcribed downstream of the Pou3f3 transcription factor gene and its depletion disrupts the differentiation of neuroblastoma cells. Locally, Dali transcript regulates transcription of the Pou3f3 locus. Distally, it preferentially targets active promoters and regulates expression of neural differentiation genes, in part through physical association with the POU3F3 protein. Dali interacts with the DNMT1 DNA methyltransferase in mouse and human and regulates DNA methylation status of CpG island-associated promoters in trans. These results demonstrate, for the first time, that a single intergenic lncRNA controls the activity and methylation of genomically distal regulatory elements to modulate large-scale transcriptional programmes.

Original languageEnglish
Pages (from-to)e04530
JournaleLIFE
Volume3
DOIs
Publication statusPublished - 21 Nov 2014

Keywords

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Chromatin
  • Conserved Sequence
  • DNA Methylation
  • Epigenesis, Genetic
  • Gene Knockdown Techniques
  • Genetic Loci
  • Humans
  • Mice, Inbred C57BL
  • Neurons
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Long Noncoding
  • RNA, Messenger
  • Transcription, Genetic

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