Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation.
BACKGROUND
Long non-protein-coding RNAs (ncRNAs) are emerging as important regulators of cellular differentiation and are widely expressed in the brain.


RESULTS
Here we show that many long ncRNAs exhibit dynamic expression patterns during neuronal and oligodendrocyte (OL) lineage specification, neuronal-glial fate transitions, and progressive stages of OL lineage elaboration including myelination. Consideration of the genomic context of these dynamically regulated ncRNAs showed they were part of complex transcriptional loci that encompass key neural developmental protein-coding genes, with which they exhibit concordant expression profiles as indicated by both microarray and in situ hybridization analyses. These included ncRNAs associated with differentiation-specific nuclear subdomains such as Gomafu and Neat1, and ncRNAs associated with developmental enhancers and genes encoding important transcription factors and homeotic proteins. We also observed changes in ncRNA expression profiles in response to treatment with trichostatin A, a histone deacetylase inhibitor that prevents the progression of OL progenitors into post-mitotic OLs by altering lineage-specific gene expression programs.


CONCLUSIONS
This is the first report of long ncRNA expression in neuronal and glial cell differentiation and of the modulation of ncRNA expression by modification of chromatin architecture. These observations explicitly link ncRNA dynamics to neural stem cell fate decisions, specification and epigenetic reprogramming and may have important implications for understanding and treating neuropsychiatric diseases.
Mercer
Tim R
TR
Institute for Molecular Bioscience, University of Queensland, 306 Carmody Road, Brisbane, QLD 4072, Australia.
Qureshi
Irfan A
IA
Gokhan
Solen
S
Dinger
Marcel E
ME
Li
Guangyu
G
Mattick
John S
JS
Mehler
Mark F
MF
D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D022661:RNA, Untranslated / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D022661:RNA, Untranslated; C012589:trichostatin A; D005680:gamma-Aminobutyric Acid