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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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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. |
format | Online Article Text |
id | pubmed-6841665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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