DEMETER plant DNA demethylase induces antiviral response by interferon signalling in animal cells

Abstract DNA methylation is a prominent epigenetic modification in plants and animals regulated by similar mechanisms but the process of DNA demethylation is profoundly different. Unlike vertebrates that require a series of enzymatic conversions of 5-methylcytosine (5mC) into other bases for DNA dem...

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Autores principales:	Young Geun Mok, Ki Young Choi, Seung Hwan Hong, Jin Hoe Huh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b9a078def3d452bbdaac6589bfe3a7a
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spelling	oai:doaj.org-article:9b9a078def3d452bbdaac6589bfe3a7a2021-12-02T15:05:42ZDEMETER plant DNA demethylase induces antiviral response by interferon signalling in animal cells10.1038/s41598-017-08827-92045-2322https://doaj.org/article/9b9a078def3d452bbdaac6589bfe3a7a2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08827-9https://doaj.org/toc/2045-2322Abstract DNA methylation is a prominent epigenetic modification in plants and animals regulated by similar mechanisms but the process of DNA demethylation is profoundly different. Unlike vertebrates that require a series of enzymatic conversions of 5-methylcytosine (5mC) into other bases for DNA demethylation, plants utilize the DEMETER (DME) family of 5mC DNA glycosylases to catalyze a direct removal of 5mC from DNA. Here we introduced Arabidopsis DME into human HEK-293T cells to allow direct 5mC excision, and observed that direct DNA demethylation activity was successfully implemented by DME expression. In addition, DME induced diverse cellular responses such as cell proliferation inhibition, cell cycle dysregulation and S phase arrest. Microarray and methylome analyses revealed that DME upregulated a number of genes including cell cycle components, heat shock proteins, and notably, various interferon-stimulated genes. Moreover, DME-mediated DNA demethylation activated endogenous repeat elements, which are likely to form dsRNAs as viral mimics and eventually trigger interferon cascades to establish the antiviral state. This work demonstrates that plant DNA demethylase catalyzes DNA demethylation with a bypass of initial base conversion steps, and the interferon signaling plays a pivotal role to alleviate genotoxic stresses associated with DME-induced DNA demethylation in mammalian cells.Young Geun MokKi Young ChoiSeung Hwan HongJin Hoe HuhNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Young Geun Mok Ki Young Choi Seung Hwan Hong Jin Hoe Huh DEMETER plant DNA demethylase induces antiviral response by interferon signalling in animal cells
description	Abstract DNA methylation is a prominent epigenetic modification in plants and animals regulated by similar mechanisms but the process of DNA demethylation is profoundly different. Unlike vertebrates that require a series of enzymatic conversions of 5-methylcytosine (5mC) into other bases for DNA demethylation, plants utilize the DEMETER (DME) family of 5mC DNA glycosylases to catalyze a direct removal of 5mC from DNA. Here we introduced Arabidopsis DME into human HEK-293T cells to allow direct 5mC excision, and observed that direct DNA demethylation activity was successfully implemented by DME expression. In addition, DME induced diverse cellular responses such as cell proliferation inhibition, cell cycle dysregulation and S phase arrest. Microarray and methylome analyses revealed that DME upregulated a number of genes including cell cycle components, heat shock proteins, and notably, various interferon-stimulated genes. Moreover, DME-mediated DNA demethylation activated endogenous repeat elements, which are likely to form dsRNAs as viral mimics and eventually trigger interferon cascades to establish the antiviral state. This work demonstrates that plant DNA demethylase catalyzes DNA demethylation with a bypass of initial base conversion steps, and the interferon signaling plays a pivotal role to alleviate genotoxic stresses associated with DME-induced DNA demethylation in mammalian cells.
format	article
author	Young Geun Mok Ki Young Choi Seung Hwan Hong Jin Hoe Huh
author_facet	Young Geun Mok Ki Young Choi Seung Hwan Hong Jin Hoe Huh
author_sort	Young Geun Mok
title	DEMETER plant DNA demethylase induces antiviral response by interferon signalling in animal cells
title_short	DEMETER plant DNA demethylase induces antiviral response by interferon signalling in animal cells
title_full	DEMETER plant DNA demethylase induces antiviral response by interferon signalling in animal cells
title_fullStr	DEMETER plant DNA demethylase induces antiviral response by interferon signalling in animal cells
title_full_unstemmed	DEMETER plant DNA demethylase induces antiviral response by interferon signalling in animal cells
title_sort	demeter plant dna demethylase induces antiviral response by interferon signalling in animal cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9b9a078def3d452bbdaac6589bfe3a7a
work_keys_str_mv	AT younggeunmok demeterplantdnademethylaseinducesantiviralresponsebyinterferonsignallinginanimalcells AT kiyoungchoi demeterplantdnademethylaseinducesantiviralresponsebyinterferonsignallinginanimalcells AT seunghwanhong demeterplantdnademethylaseinducesantiviralresponsebyinterferonsignallinginanimalcells AT jinhoehuh demeterplantdnademethylaseinducesantiviralresponsebyinterferonsignallinginanimalcells
_version_	1718388720616341504

DEMETER plant DNA demethylase induces antiviral response by interferon signalling in animal cells

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