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HERVH-derived lncRNAs negatively regulate chromatin targeting and remodeling mediated by CHD7
Chd7 encodes an ATP-dependent chromatin remodeler which has been shown to target specific genomic loci and alter local transcription potentially by remodeling chromatin structure. De novo mutations in CHD7 are the major cause of CHARGE syndrome which features multiple developmental defects. We exami...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548210/ https://www.ncbi.nlm.nih.gov/pubmed/34663690 http://dx.doi.org/10.26508/lsa.202101127 |
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author | Hsieh, Fu-Kai Ji, Fei Damle, Manashree Sadreyev, Ruslan I Kingston, Robert E |
author_facet | Hsieh, Fu-Kai Ji, Fei Damle, Manashree Sadreyev, Ruslan I Kingston, Robert E |
author_sort | Hsieh, Fu-Kai |
collection | PubMed |
description | Chd7 encodes an ATP-dependent chromatin remodeler which has been shown to target specific genomic loci and alter local transcription potentially by remodeling chromatin structure. De novo mutations in CHD7 are the major cause of CHARGE syndrome which features multiple developmental defects. We examined whether nuclear RNAs might contribute to its targeting and function and identified a preferential interaction between CHD7 and lncRNAs derived from HERVH loci in pluripotent stem cells. Knockdown of HERVH family lncRNAs using LNAs or knockout of an individual copy of HERVH by CRISPR-Cas9 both resulted in increased binding of CHD7 and increased levels of H3K27ac at a subset of enhancers. Depletion of HERVH family RNAs led to the activation of multiple genes. CHD7 bound HERVH RNA with high affinity but low specificity and this interaction decreased the ability of CHD7 to bind and remodel nucleosomes. We present a model in which HERVH lncRNAs act as a decoy to modulate the dynamics of CHD7 binding to enhancers in pluripotent cells and the activation of numerous genes that might impact the differentiation process. |
format | Online Article Text |
id | pubmed-8548210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-85482102021-11-05 HERVH-derived lncRNAs negatively regulate chromatin targeting and remodeling mediated by CHD7 Hsieh, Fu-Kai Ji, Fei Damle, Manashree Sadreyev, Ruslan I Kingston, Robert E Life Sci Alliance Research Articles Chd7 encodes an ATP-dependent chromatin remodeler which has been shown to target specific genomic loci and alter local transcription potentially by remodeling chromatin structure. De novo mutations in CHD7 are the major cause of CHARGE syndrome which features multiple developmental defects. We examined whether nuclear RNAs might contribute to its targeting and function and identified a preferential interaction between CHD7 and lncRNAs derived from HERVH loci in pluripotent stem cells. Knockdown of HERVH family lncRNAs using LNAs or knockout of an individual copy of HERVH by CRISPR-Cas9 both resulted in increased binding of CHD7 and increased levels of H3K27ac at a subset of enhancers. Depletion of HERVH family RNAs led to the activation of multiple genes. CHD7 bound HERVH RNA with high affinity but low specificity and this interaction decreased the ability of CHD7 to bind and remodel nucleosomes. We present a model in which HERVH lncRNAs act as a decoy to modulate the dynamics of CHD7 binding to enhancers in pluripotent cells and the activation of numerous genes that might impact the differentiation process. Life Science Alliance LLC 2021-10-18 /pmc/articles/PMC8548210/ /pubmed/34663690 http://dx.doi.org/10.26508/lsa.202101127 Text en © 2021 Hsieh et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Hsieh, Fu-Kai Ji, Fei Damle, Manashree Sadreyev, Ruslan I Kingston, Robert E HERVH-derived lncRNAs negatively regulate chromatin targeting and remodeling mediated by CHD7 |
title | HERVH-derived lncRNAs negatively regulate chromatin targeting and remodeling mediated by CHD7 |
title_full | HERVH-derived lncRNAs negatively regulate chromatin targeting and remodeling mediated by CHD7 |
title_fullStr | HERVH-derived lncRNAs negatively regulate chromatin targeting and remodeling mediated by CHD7 |
title_full_unstemmed | HERVH-derived lncRNAs negatively regulate chromatin targeting and remodeling mediated by CHD7 |
title_short | HERVH-derived lncRNAs negatively regulate chromatin targeting and remodeling mediated by CHD7 |
title_sort | hervh-derived lncrnas negatively regulate chromatin targeting and remodeling mediated by chd7 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548210/ https://www.ncbi.nlm.nih.gov/pubmed/34663690 http://dx.doi.org/10.26508/lsa.202101127 |
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