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Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability

Chromodomain helicase DNA binding protein 2 (Chd2) is a chromatin remodeller implicated in neurological disease. Here we show that Chaserr, a highly conserved long noncoding RNA transcribed from a region near the transcription start site of Chd2 and on the same strand, acts in concert with the CHD2...

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Autores principales: Rom, Aviv, Melamed, Liliya, Gil, Noa, Goldrich, Micah Jonathan, Kadir, Rotem, Golan, Matan, Biton, Inbal, Perry, Rotem Ben-Tov, Ulitsky, Igor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6841665/
https://www.ncbi.nlm.nih.gov/pubmed/31704914
http://dx.doi.org/10.1038/s41467-019-13075-8
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author Rom, Aviv
Melamed, Liliya
Gil, Noa
Goldrich, Micah Jonathan
Kadir, Rotem
Golan, Matan
Biton, Inbal
Perry, Rotem Ben-Tov
Ulitsky, Igor
author_facet Rom, Aviv
Melamed, Liliya
Gil, Noa
Goldrich, Micah Jonathan
Kadir, Rotem
Golan, Matan
Biton, Inbal
Perry, Rotem Ben-Tov
Ulitsky, Igor
author_sort Rom, Aviv
collection PubMed
description Chromodomain helicase DNA binding protein 2 (Chd2) is a chromatin remodeller implicated in neurological disease. Here we show that Chaserr, a highly conserved long noncoding RNA transcribed from a region near the transcription start site of Chd2 and on the same strand, acts in concert with the CHD2 protein to maintain proper Chd2 expression levels. Loss of Chaserr in mice leads to early postnatal lethality in homozygous mice, and severe growth retardation in heterozygotes. Mechanistically, loss of Chaserr leads to substantially increased Chd2 mRNA and protein levels, which in turn lead to transcriptional interference by inhibiting promoters found downstream of highly expressed genes. We further show that Chaserr production represses Chd2 expression solely in cis, and that the phenotypic consequences of Chaserr loss are rescued when Chd2 is perturbed as well. Targeting Chaserr is thus a potential strategy for increasing CHD2 levels in haploinsufficient individuals.
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spelling pubmed-68416652019-11-13 Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability Rom, Aviv Melamed, Liliya Gil, Noa Goldrich, Micah Jonathan Kadir, Rotem Golan, Matan Biton, Inbal Perry, Rotem Ben-Tov Ulitsky, Igor Nat Commun Article Chromodomain helicase DNA binding protein 2 (Chd2) is a chromatin remodeller implicated in neurological disease. Here we show that Chaserr, a highly conserved long noncoding RNA transcribed from a region near the transcription start site of Chd2 and on the same strand, acts in concert with the CHD2 protein to maintain proper Chd2 expression levels. Loss of Chaserr in mice leads to early postnatal lethality in homozygous mice, and severe growth retardation in heterozygotes. Mechanistically, loss of Chaserr leads to substantially increased Chd2 mRNA and protein levels, which in turn lead to transcriptional interference by inhibiting promoters found downstream of highly expressed genes. We further show that Chaserr production represses Chd2 expression solely in cis, and that the phenotypic consequences of Chaserr loss are rescued when Chd2 is perturbed as well. Targeting Chaserr is thus a potential strategy for increasing CHD2 levels in haploinsufficient individuals. Nature Publishing Group UK 2019-11-08 /pmc/articles/PMC6841665/ /pubmed/31704914 http://dx.doi.org/10.1038/s41467-019-13075-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Rom, Aviv
Melamed, Liliya
Gil, Noa
Goldrich, Micah Jonathan
Kadir, Rotem
Golan, Matan
Biton, Inbal
Perry, Rotem Ben-Tov
Ulitsky, Igor
Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability
title Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability
title_full Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability
title_fullStr Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability
title_full_unstemmed Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability
title_short Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability
title_sort regulation of chd2 expression by the chaserr long noncoding rna gene is essential for viability
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6841665/
https://www.ncbi.nlm.nih.gov/pubmed/31704914
http://dx.doi.org/10.1038/s41467-019-13075-8
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