The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes

The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes

Abstract Genome-wide studies have uncovered specific genetic alterations, transcriptomic patterns and epigenetic profiles associated with different glioma types. We have recently created a unique atlas encompassing genome-wide profiles of open chromatin, histone H3K27ac and H3Kme3 modifications, DNA...

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Autores principales: Ilona E. Grabowicz, Bartek Wilczyński, Bożena Kamińska, Adria-Jaume Roura, Bartosz Wojtaś, Michał J. Dąbrowski
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Science
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Acceso en línea:https://doaj.org/article/d37f7725572f4d429f882dde4a079fc8
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spelling oai:doaj.org-article:d37f7725572f4d429f882dde4a079fc82021-12-02T16:35:28ZThe role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes10.1038/s41598-021-95009-32045-2322https://doaj.org/article/d37f7725572f4d429f882dde4a079fc82021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95009-3https://doaj.org/toc/2045-2322Abstract Genome-wide studies have uncovered specific genetic alterations, transcriptomic patterns and epigenetic profiles associated with different glioma types. We have recently created a unique atlas encompassing genome-wide profiles of open chromatin, histone H3K27ac and H3Kme3 modifications, DNA methylation and transcriptomes of 33 glioma samples of different grades. Here, we intersected genome-wide atlas data with topologically associating domains (TADs) and demonstrated that the chromatin organization and epigenetic landscape of enhancers have a strong impact on genes differentially expressed in WHO low grade versus high grade gliomas. We identified TADs enriched in glioma grade-specific genes and/or epigenetic marks. We found the set of transcription factors, including REST, E2F1 and NFKB1, that are most likely to regulate gene expression in multiple TADs, containing specific glioma-related genes. Moreover, many genes associated with the cell–matrix adhesion Gene Ontology group, in particular 14 PROTOCADHERINs, were found to be regulated by long-range contacts with enhancers. Presented results demonstrate the existence of epigenetic differences associated with chromatin organization driving differential gene expression in gliomas of different malignancy.Ilona E. GrabowiczBartek WilczyńskiBożena KamińskaAdria-Jaume RouraBartosz WojtaśMichał J. DąbrowskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ilona E. Grabowicz
Bartek Wilczyński
Bożena Kamińska
Adria-Jaume Roura
Bartosz Wojtaś
Michał J. Dąbrowski
The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes
description Abstract Genome-wide studies have uncovered specific genetic alterations, transcriptomic patterns and epigenetic profiles associated with different glioma types. We have recently created a unique atlas encompassing genome-wide profiles of open chromatin, histone H3K27ac and H3Kme3 modifications, DNA methylation and transcriptomes of 33 glioma samples of different grades. Here, we intersected genome-wide atlas data with topologically associating domains (TADs) and demonstrated that the chromatin organization and epigenetic landscape of enhancers have a strong impact on genes differentially expressed in WHO low grade versus high grade gliomas. We identified TADs enriched in glioma grade-specific genes and/or epigenetic marks. We found the set of transcription factors, including REST, E2F1 and NFKB1, that are most likely to regulate gene expression in multiple TADs, containing specific glioma-related genes. Moreover, many genes associated with the cell–matrix adhesion Gene Ontology group, in particular 14 PROTOCADHERINs, were found to be regulated by long-range contacts with enhancers. Presented results demonstrate the existence of epigenetic differences associated with chromatin organization driving differential gene expression in gliomas of different malignancy.
format article
author Ilona E. Grabowicz
Bartek Wilczyński
Bożena Kamińska
Adria-Jaume Roura
Bartosz Wojtaś
Michał J. Dąbrowski
author_facet Ilona E. Grabowicz
Bartek Wilczyński
Bożena Kamińska
Adria-Jaume Roura
Bartosz Wojtaś
Michał J. Dąbrowski
author_sort Ilona E. Grabowicz
title The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes
title_short The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes
title_full The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes
title_fullStr The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes
title_full_unstemmed The role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes
title_sort role of epigenetic modifications, long-range contacts, enhancers and topologically associating domains in the regulation of glioma grade-specific genes
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/d37f7725572f4d429f882dde4a079fc8
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