Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in Glioblastoma
Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor in adulthood. Epigenetic mechanisms are known to play a key role in GBM although the involvement of histone methyltransferase KMT5B and its mark H4K20me2 has remained largely unexplored. The present study shows that...
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Format: | Article |
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Frontiers Media S.A.
2021-08-01
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Series: | Frontiers in Cell and Developmental Biology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.671838/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Virginia López Juan Ramón Tejedor Antonella Carella María G. García Pablo Santamarina-Ojeda Raúl F. Pérez Cristina Mangas Rocío G. Urdinguio Aitziber Aranburu Daniel de la Nava María D. Corte-Torres Aurora Astudillo Manuela Mollejo Bárbara Meléndez Agustín F. Fernández Mario F. Fraga |
spellingShingle |
Virginia López Juan Ramón Tejedor Antonella Carella María G. García Pablo Santamarina-Ojeda Raúl F. Pérez Cristina Mangas Rocío G. Urdinguio Aitziber Aranburu Daniel de la Nava María D. Corte-Torres Aurora Astudillo Manuela Mollejo Bárbara Meléndez Agustín F. Fernández Mario F. Fraga Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in Glioblastoma Frontiers in Cell and Developmental Biology epigenetics glioblastoma histone methyltransferase histone posttranslational modification tumor suppressor |
author_facet |
Virginia López Juan Ramón Tejedor Antonella Carella María G. García Pablo Santamarina-Ojeda Raúl F. Pérez Cristina Mangas Rocío G. Urdinguio Aitziber Aranburu Daniel de la Nava María D. Corte-Torres Aurora Astudillo Manuela Mollejo Bárbara Meléndez Agustín F. Fernández Mario F. Fraga |
author_sort |
Virginia López |
title |
Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in Glioblastoma |
title_short |
Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in Glioblastoma |
title_full |
Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in Glioblastoma |
title_fullStr |
Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in Glioblastoma |
title_full_unstemmed |
Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in Glioblastoma |
title_sort |
epigenetic deregulation of the histone methyltransferase kmt5b contributes to malignant transformation in glioblastoma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-08-01 |
description |
Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor in adulthood. Epigenetic mechanisms are known to play a key role in GBM although the involvement of histone methyltransferase KMT5B and its mark H4K20me2 has remained largely unexplored. The present study shows that DNA hypermethylation and loss of DNA hydroxymethylation is associated with KMT5B downregulation and genome-wide reduction of H4K20me2 levels in a set of human GBM samples and cell lines as compared with non-tumoral specimens. Ectopic overexpression of KMT5B induced tumor suppressor-like features in vitro and in a mouse tumor xenograft model, as well as changes in the expression of several glioblastoma-related genes. H4K20me2 enrichment was found immediately upstream of the promoter regions of a subset of deregulated genes, thus suggesting a possible role for KMT5B in GBM through the epigenetic modulation of key target cancer genes. |
topic |
epigenetics glioblastoma histone methyltransferase histone posttranslational modification tumor suppressor |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.671838/full |
work_keys_str_mv |
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doaj-ec4338a095514184a29503d3b2538b892021-08-10T07:24:01ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-08-01910.3389/fcell.2021.671838671838Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in GlioblastomaVirginia López0Juan Ramón Tejedor1Antonella Carella2María G. García3Pablo Santamarina-Ojeda4Raúl F. Pérez5Cristina Mangas6Rocío G. Urdinguio7Aitziber Aranburu8Daniel de la Nava9María D. Corte-Torres10Aurora Astudillo11Manuela Mollejo12Bárbara Meléndez13Agustín F. Fernández14Mario F. Fraga15Cancer Epigenetics and Nanomedicine Laboratory, Department of Organisms and Systems Biology, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Rare Diseases CIBER (CIBERER) of the Carlos III Health Institute (ISCIII), University of Oviedo, Oviedo, SpainCancer Epigenetics and Nanomedicine Laboratory, Department of Organisms and Systems Biology, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Rare Diseases CIBER (CIBERER) of the Carlos III Health Institute (ISCIII), University of Oviedo, Oviedo, SpainCancer Epigenetics and Nanomedicine Laboratory, Department of Organisms and Systems Biology, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Rare Diseases CIBER (CIBERER) of the Carlos III Health Institute (ISCIII), University of Oviedo, Oviedo, SpainCancer Epigenetics and Nanomedicine Laboratory, Department of Organisms and Systems Biology, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Rare Diseases CIBER (CIBERER) of the Carlos III Health Institute (ISCIII), University of Oviedo, Oviedo, SpainCancer Epigenetics and Nanomedicine Laboratory, Department of Organisms and Systems Biology, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Rare Diseases CIBER (CIBERER) of the Carlos III Health Institute (ISCIII), University of Oviedo, Oviedo, SpainCancer Epigenetics and Nanomedicine Laboratory, Department of Organisms and Systems Biology, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Rare Diseases CIBER (CIBERER) of the Carlos III Health Institute (ISCIII), University of Oviedo, Oviedo, SpainCancer Epigenetics and Nanomedicine Laboratory, Department of Organisms and Systems Biology, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Rare Diseases CIBER (CIBERER) of the Carlos III Health Institute (ISCIII), University of Oviedo, Oviedo, SpainCancer Epigenetics and Nanomedicine Laboratory, Department of Organisms and Systems Biology, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Rare Diseases CIBER (CIBERER) of the Carlos III Health Institute (ISCIII), University of Oviedo, Oviedo, SpainCancer Epigenetics and Nanomedicine Laboratory, Department of Organisms and Systems Biology, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Rare Diseases CIBER (CIBERER) of the Carlos III Health Institute (ISCIII), University of Oviedo, Oviedo, SpainCancer Epigenetics and Nanomedicine Laboratory, Department of Organisms and Systems Biology, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Rare Diseases CIBER (CIBERER) of the Carlos III Health Institute (ISCIII), University of Oviedo, Oviedo, SpainBiobanco del Principado de Asturias, Hospital Universitario Central de Asturias (HUCA), Oviedo, SpainDepartamento de Anatomía Patológica, Hospital Universitario Central de Asturias (HUCA), Oviedo, SpainDepartamento de Patología, Hospital Virgen de la Salud (CHT), Toledo, SpainDepartamento de Patología, Hospital Virgen de la Salud (CHT), Toledo, SpainCancer Epigenetics and Nanomedicine Laboratory, Department of Organisms and Systems Biology, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Rare Diseases CIBER (CIBERER) of the Carlos III Health Institute (ISCIII), University of Oviedo, Oviedo, SpainCancer Epigenetics and Nanomedicine Laboratory, Department of Organisms and Systems Biology, Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Health Research Institute of Asturias (ISPA), Institute of Oncology of Asturias (IUOPA), Rare Diseases CIBER (CIBERER) of the Carlos III Health Institute (ISCIII), University of Oviedo, Oviedo, SpainGlioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor in adulthood. Epigenetic mechanisms are known to play a key role in GBM although the involvement of histone methyltransferase KMT5B and its mark H4K20me2 has remained largely unexplored. The present study shows that DNA hypermethylation and loss of DNA hydroxymethylation is associated with KMT5B downregulation and genome-wide reduction of H4K20me2 levels in a set of human GBM samples and cell lines as compared with non-tumoral specimens. Ectopic overexpression of KMT5B induced tumor suppressor-like features in vitro and in a mouse tumor xenograft model, as well as changes in the expression of several glioblastoma-related genes. H4K20me2 enrichment was found immediately upstream of the promoter regions of a subset of deregulated genes, thus suggesting a possible role for KMT5B in GBM through the epigenetic modulation of key target cancer genes.https://www.frontiersin.org/articles/10.3389/fcell.2021.671838/fullepigeneticsglioblastomahistone methyltransferasehistone posttranslational modificationtumor suppressor |