DEMETER plant DNA demethylase induces antiviral response by interferonsignalling in animal cells
| Autor: | Seung Hwan Hong, Young Geun Mok, Kiyoung Choi, Jin Hoe Huh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Science Arabidopsis Article Epigenesis Genetic S Phase 03 medical and health sciences chemistry.chemical_compound Humans Epigenetics N-Glycosyl Hydrolases Cell Proliferation Oligonucleotide Array Sequence Analysis Multidisciplinary biology Arabidopsis Proteins Cell Cycle Cell cycle DNA Methylation Up-Regulation 5-Methylcytosine 030104 developmental biology DNA demethylation HEK293 Cells chemistry Biochemistry Gene Expression Regulation DNA glycosylase DNA methylation biology.protein Trans-Activators Demethylase Medicine Interferons DNA Signal Transduction |
| Zdroj: | SCIENTIFIC REPORTS(7) Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) Scientific Reports |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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