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

  1. Vladislava Chalei
  2. Stephen N Sansom
  3. Lesheng Kong
  4. Sheena Lee
  5. Juan Montiel
  6. Keith W Vance
  7. Chris P Ponting  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. Oxford University, United Kingdom
  3. University of Bath, United Kingdom

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.

Article and author information

Author details

  1. Vladislava Chalei

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  2. Stephen N Sansom

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  3. Lesheng Kong

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  4. Sheena Lee

    Oxford University, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  5. Juan Montiel

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  6. Keith W Vance

    University of Bath, Bath, United Kingdom
    Competing interests
    No competing interests declared.
  7. Chris P Ponting

    University of Oxford, Oxford, United Kingdom
    For correspondence
    Chris.Ponting@dpag.ox.ac.uk
    Competing interests
    Chris P Ponting, Senior editor, eLife.

Ethics

Animal experimentation: All animal experiments were conducted in accordance to schedule one UK Home Office guidelines (Scientific Procedures Act, 1986).

Reviewing Editor

  1. Thomas R Gingeras, Cold Spring Harbor Laboratory, United States

Publication history

  1. Received: August 28, 2014
  2. Accepted: November 21, 2014
  3. Accepted Manuscript published: November 21, 2014 (version 1)
  4. Version of Record published: December 16, 2014 (version 2)

Copyright

© 2014, Chalei et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Vladislava Chalei
  2. Stephen N Sansom
  3. Lesheng Kong
  4. Sheena Lee
  5. Juan Montiel
  6. Keith W Vance
  7. Chris P Ponting
(2014)
The long non-coding RNA Dali is an epigenetic regulator of neural differentiation
eLife 3:e04530.
https://doi.org/10.7554/eLife.04530

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