NDLI: Genome-Wide Screen of DNA Methylation Changes Induced by Low Dose X-Ray Radiation in Mice

Content Provider	PubMed Central
Author	Wang, Jingzi Zhang, Youwei Kai, Xu Mao, Xiaobei Xue, Lijun Liu, Xiaobei Yu, Hongjun Chen, Longbang Chu, Xiaoyuan
Editor	Castresana, Javier S.
Copyright Year	2014
Abstract	Epigenetic mechanisms play a key role in non-targeted effects of radiation. The purpose of this study was to investigate global hypomethylation and promoter hypermethylation of particular genes induced by low dose radiation (LDR). Thirty male BALB/c mice were divided into 3 groups: control, acutely exposed (0.5Gy X-rays), and chronic exposure for 10 days (0.05Gy/d×10d). High-performance liquid chromatography (HPLC) and MeDIP-quantitative polymerase chain reaction (qPCR) were used to study methylation profiles. DNMT1 and MBD2 expression was determined by qPCR and western blot assays. Methylation and expression of Rad23b and Ddit3 were determined by bisulfate sequencing primers (BSP) and qPCR, respectively. The results show that LDR induced genomic hypomethylation in blood 2 h postirraditaion, but was not retained at 1-month. DNMT1 and MBD2 were downregulated in a tissue-specific manner but did not persist. Specific hypermethylation was observed for 811 regions in the group receiving chronic exposure, which covered almost all key biological processes as indicated by GO and KEGG pathway analysis. Eight hypermethylated genes (Rad23b, Tdg, Ccnd1, Ddit3, Llgl1, Rasl11a, Tbx2, Scl6a15) were verified by MeDIP-qPCR. Among them, Rad23b and Ddit3 gene displayed tissue-specific methylation and downregulation, which persisted for 1-month postirradiation. Thus, LDR induced global hypomethylation and tissue-specific promoter hypermethylation of particular genes. Promoter hypermethylation, rather than global hypomethylation, was relatively stable. Dysregulation of methylation might be correlated with down-regulation of DNMT1 and MBD2, but much better understanding the molecular mechanisms involved in this process will require further study.
Related Links	http://dx.doi.org/10.1371/journal.pone.0090804
Starting Page	90804
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	3
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-03-10
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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