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TALE-directed local modulation of H3K9 methylation shapes exon recognition
In search for the function of local chromatin environment on pre-mRNA processing we established a new tool, which allows for the modification of chromatin using a targeted approach. Using Transcription Activator-Like Effector domains fused to histone modifying enzymes (TALE-HME), we show locally res...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4954949/ https://www.ncbi.nlm.nih.gov/pubmed/27439481 http://dx.doi.org/10.1038/srep29961 |
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author | Bieberstein, Nicole I. Kozáková, Eva Huranová, Martina Thakur, Prasoon K. Krchňáková, Zuzana Krausová, Michaela Oesterreich, Fernando Carrillo Staněk, David |
author_facet | Bieberstein, Nicole I. Kozáková, Eva Huranová, Martina Thakur, Prasoon K. Krchňáková, Zuzana Krausová, Michaela Oesterreich, Fernando Carrillo Staněk, David |
author_sort | Bieberstein, Nicole I. |
collection | PubMed |
description | In search for the function of local chromatin environment on pre-mRNA processing we established a new tool, which allows for the modification of chromatin using a targeted approach. Using Transcription Activator-Like Effector domains fused to histone modifying enzymes (TALE-HME), we show locally restricted alteration of histone methylation modulates the splicing of target exons. We provide evidence that a local increase in H3K9 di- and trimethylation promotes inclusion of the target alternative exon, while demethylation by JMJD2D leads to exon skipping. We further demonstrate that H3K9me3 is localized on internal exons genome-wide suggesting a general role in splicing. Consistently, targeting of the H3K9 demethylase to a weak constitutive exon reduced co-transcriptional splicing. Together our data show H3K9 methylation within the gene body is a factor influencing recognition of both constitutive and alternative exons. |
format | Online Article Text |
id | pubmed-4954949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49549492016-07-26 TALE-directed local modulation of H3K9 methylation shapes exon recognition Bieberstein, Nicole I. Kozáková, Eva Huranová, Martina Thakur, Prasoon K. Krchňáková, Zuzana Krausová, Michaela Oesterreich, Fernando Carrillo Staněk, David Sci Rep Article In search for the function of local chromatin environment on pre-mRNA processing we established a new tool, which allows for the modification of chromatin using a targeted approach. Using Transcription Activator-Like Effector domains fused to histone modifying enzymes (TALE-HME), we show locally restricted alteration of histone methylation modulates the splicing of target exons. We provide evidence that a local increase in H3K9 di- and trimethylation promotes inclusion of the target alternative exon, while demethylation by JMJD2D leads to exon skipping. We further demonstrate that H3K9me3 is localized on internal exons genome-wide suggesting a general role in splicing. Consistently, targeting of the H3K9 demethylase to a weak constitutive exon reduced co-transcriptional splicing. Together our data show H3K9 methylation within the gene body is a factor influencing recognition of both constitutive and alternative exons. Nature Publishing Group 2016-07-21 /pmc/articles/PMC4954949/ /pubmed/27439481 http://dx.doi.org/10.1038/srep29961 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Bieberstein, Nicole I. Kozáková, Eva Huranová, Martina Thakur, Prasoon K. Krchňáková, Zuzana Krausová, Michaela Oesterreich, Fernando Carrillo Staněk, David TALE-directed local modulation of H3K9 methylation shapes exon recognition |
title | TALE-directed local modulation of H3K9 methylation shapes exon recognition |
title_full | TALE-directed local modulation of H3K9 methylation shapes exon recognition |
title_fullStr | TALE-directed local modulation of H3K9 methylation shapes exon recognition |
title_full_unstemmed | TALE-directed local modulation of H3K9 methylation shapes exon recognition |
title_short | TALE-directed local modulation of H3K9 methylation shapes exon recognition |
title_sort | tale-directed local modulation of h3k9 methylation shapes exon recognition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4954949/ https://www.ncbi.nlm.nih.gov/pubmed/27439481 http://dx.doi.org/10.1038/srep29961 |
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