VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation

Abstract VHL inactivation is a key oncogenic event for renal carcinomas. In normoxia, VHL suppresses HIF1a-mediated transcriptional response, which is characteristic to hypoxia. It has previously been shown that hypoxic conditions inhibit TET-dependent hydroxymethylation of cytosines and cause DNA h...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Artem V. Artemov, Nadezhda Zhigalova, Svetlana Zhenilo, Alexander M. Mazur, Egor B. Prokhortchouk
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/15befa2463bd4422a26c6f55bc7ff062
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:15befa2463bd4422a26c6f55bc7ff062
record_format	dspace
spelling	oai:doaj.org-article:15befa2463bd4422a26c6f55bc7ff0622021-12-02T15:08:37ZVHL inactivation without hypoxia is sufficient to achieve genome hypermethylation10.1038/s41598-018-28795-y2045-2322https://doaj.org/article/15befa2463bd4422a26c6f55bc7ff0622018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28795-yhttps://doaj.org/toc/2045-2322Abstract VHL inactivation is a key oncogenic event for renal carcinomas. In normoxia, VHL suppresses HIF1a-mediated transcriptional response, which is characteristic to hypoxia. It has previously been shown that hypoxic conditions inhibit TET-dependent hydroxymethylation of cytosines and cause DNA hypermethylation at gene promoters. In this work, we performed VHL inactivation by CRISPR/Cas9 and studied its effects on gene expression and DNA methylation. We showed that even without hypoxia, VHL inactivation leads to hypermethylation of the genome. Hypermethylated cytosines were evenly distributed throughout the genome with a slight preference for AP-1 (JUN and FOS) binding sites. Hypermethylated cytosines tended to be enriched within the binding sites of transcription factors that showed increased gene expression after VHL inactivation. We also observed promoter hypermethylation associated with decreased gene expression for several regulators of transcription and DNA methylation including SALL3.Artem V. ArtemovNadezhda ZhigalovaSvetlana ZheniloAlexander M. MazurEgor B. ProkhortchoukNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-7 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Artem V. Artemov Nadezhda Zhigalova Svetlana Zhenilo Alexander M. Mazur Egor B. Prokhortchouk VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation
description	Abstract VHL inactivation is a key oncogenic event for renal carcinomas. In normoxia, VHL suppresses HIF1a-mediated transcriptional response, which is characteristic to hypoxia. It has previously been shown that hypoxic conditions inhibit TET-dependent hydroxymethylation of cytosines and cause DNA hypermethylation at gene promoters. In this work, we performed VHL inactivation by CRISPR/Cas9 and studied its effects on gene expression and DNA methylation. We showed that even without hypoxia, VHL inactivation leads to hypermethylation of the genome. Hypermethylated cytosines were evenly distributed throughout the genome with a slight preference for AP-1 (JUN and FOS) binding sites. Hypermethylated cytosines tended to be enriched within the binding sites of transcription factors that showed increased gene expression after VHL inactivation. We also observed promoter hypermethylation associated with decreased gene expression for several regulators of transcription and DNA methylation including SALL3.
format	article
author	Artem V. Artemov Nadezhda Zhigalova Svetlana Zhenilo Alexander M. Mazur Egor B. Prokhortchouk
author_facet	Artem V. Artemov Nadezhda Zhigalova Svetlana Zhenilo Alexander M. Mazur Egor B. Prokhortchouk
author_sort	Artem V. Artemov
title	VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation
title_short	VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation
title_full	VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation
title_fullStr	VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation
title_full_unstemmed	VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation
title_sort	vhl inactivation without hypoxia is sufficient to achieve genome hypermethylation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/15befa2463bd4422a26c6f55bc7ff062
work_keys_str_mv	AT artemvartemov vhlinactivationwithouthypoxiaissufficienttoachievegenomehypermethylation AT nadezhdazhigalova vhlinactivationwithouthypoxiaissufficienttoachievegenomehypermethylation AT svetlanazhenilo vhlinactivationwithouthypoxiaissufficienttoachievegenomehypermethylation AT alexandermmazur vhlinactivationwithouthypoxiaissufficienttoachievegenomehypermethylation AT egorbprokhortchouk vhlinactivationwithouthypoxiaissufficienttoachievegenomehypermethylation
_version_	1718388044371853312

VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation

Ejemplares similares