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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, ne...

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Autores principales: Mercer, Tim R, Qureshi, Irfan A, Gokhan, Solen, Dinger, Marcel E, Li, Guangyu, Mattick, John S, Mehler, Mark F
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829031/
https://www.ncbi.nlm.nih.gov/pubmed/20137068
http://dx.doi.org/10.1186/1471-2202-11-14
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author Mercer, Tim R
Qureshi, Irfan A
Gokhan, Solen
Dinger, Marcel E
Li, Guangyu
Mattick, John S
Mehler, Mark F
author_facet Mercer, Tim R
Qureshi, Irfan A
Gokhan, Solen
Dinger, Marcel E
Li, Guangyu
Mattick, John S
Mehler, Mark F
author_sort Mercer, Tim R
collection PubMed
description 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. CONCLUSION: 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.
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spelling pubmed-28290312010-02-26 Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation Mercer, Tim R Qureshi, Irfan A Gokhan, Solen Dinger, Marcel E Li, Guangyu Mattick, John S Mehler, Mark F BMC Neurosci Research article 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. CONCLUSION: 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. BioMed Central 2010-02-05 /pmc/articles/PMC2829031/ /pubmed/20137068 http://dx.doi.org/10.1186/1471-2202-11-14 Text en Copyright ©2010 Mercer et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research article
Mercer, Tim R
Qureshi, Irfan A
Gokhan, Solen
Dinger, Marcel E
Li, Guangyu
Mattick, John S
Mehler, Mark F
Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation
title Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation
title_full Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation
title_fullStr Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation
title_full_unstemmed Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation
title_short Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation
title_sort long noncoding rnas in neuronal-glial fate specification and oligodendrocyte lineage maturation
topic Research article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829031/
https://www.ncbi.nlm.nih.gov/pubmed/20137068
http://dx.doi.org/10.1186/1471-2202-11-14
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