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PMID: 25415054 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

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

eLife ·Vol. 3 ·2014-11-21 ·Pages e04530

Chalei V, Sansom SN, Kong L, Lee S, Montiel JF, Vance KW, Ponting CP

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.

Keywords
DALIR DNA methylation DNMT1 Pou3f3 biochemistry chromatin chromosomes genes human lncRNA mouse transcription
MeSH Terms
Animals Cell Differentiation/genetics Cell Lineage/genetics Chromatin/metabolism Conserved Sequence/genetics DNA Methylation/genetics Epigenesis, Genetic Gene Knockdown Techniques Genetic Loci Humans Mice, Inbred C57BL Neurons/cytology,metabolism Promoter Regions, Genetic Protein Binding/genetics RNA, Long Noncoding/genetics,metabolism RNA, Messenger/metabolism Transcription, Genetic
Chemicals
Chromatin Dali long noncoding RNA, mouse RNA, Long Noncoding RNA, Messenger
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Chalei Vladislava
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Sansom Stephen N
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Kong Lesheng
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Lee Sheena
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Montiel Juan F
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Vance Keith W
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Ponting Chris P
MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
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Article Info
Journal
eLife
Abbr.
Elife
ISSN
2050-084X
DOI
10.7554/eLife.04530
Published
2014-11-21
Epub
2014-00-21
Pages
e04530
Language
English
Region
England
NLM ID
101579614
PMCID
PMC4383022
Subset
IM
Grants
Medical Research Council · MC_UU_12021/1 · United Kingdom
Medical Research Council · MC_U137761446 · United Kingdom
Wellcome Trust · 090532/Z/09/Z · United Kingdom
Medical Research Council · MC_EX_UU_G1000902 · United Kingdom
European Research Council · 249869 · International
Medical Research Council · G0900747 91070 · United Kingdom
Wellcome Trust · 084655 · United Kingdom
Databases
GEO
GSE62035
External Links
PubMed source DOI: 10.7554/eLife.04530 PMC Full Text View journal details
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