Gestational arsenic exposure induces site-specific DNA hypomethylation in active retrotransposon subfamilies in offsprin
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Epigenetics & Chromatin Open Access
RESEARCH
Gestational arsenic exposure induces site‑specific DNA hypomethylation in active retrotransposon subfamilies in offspring sperm in mice Keiko Nohara1* , Kazuhiko Nakabayashi2, Kazuyuki Okamura1, Takehiro Suzuki1, Shigekatsu Suzuki3 and Kenichiro Hata2
Abstract Background: Environmental impacts on a fetus can disrupt germ cell development leading to epimutations in mature germ cells. Paternal inheritance of adverse health effects through sperm epigenomes, including DNA methylomes, has been recognized in human and animal studies. However, the impacts of gestational exposure to a variety of environmental factors on the germ cell epigenomes are not fully investigated. Arsenic, a naturally occurring contaminant, is one of the most concerning environmental chemicals, that is causing serious health problems, including an increase in cancer, in highly contaminated areas worldwide. We previously showed that gestational arsenic exposure of pregnant C3H mice paternally induces hepatic tumor increase in the second generation (F2). In the present study, we have investigated the F1 sperm DNA methylomes genome-widely by one-base resolution analysis using a reduced representation bisulfite sequencing (RRBS) method. Results: We have clarified that gestational arsenic exposure increases hypomethylated cytosines in all the chromosomes and they are significantly overrepresented in the retrotransposon LINEs and LTRs, predominantly in the intergenic regions. Closer analyses of detailed annotated DNA sequences showed that hypomethylated cytosines are especially accumulated in the promoter regions of the active full-length L1MdA subfamily in LINEs, and 5′LTRs of the active IAPE subfamily in LTRs. This is the first report that has identified the specific positions of methylomes altered in the retrotransposon elements by environmental exposure, by genome-wide methylome analysis. Conclusion: Lowered DNA methylation potentially enhances L1MdA retrotransposition and cryptic promoter activity of 5′LTR for coding genes and non-coding RNAs. The present study has illuminated the environmental impacts on sperm DNA methylome establishment that can lead to augmented retrotransposon activities in germ cells and can cause harmful effects in the following generation. Keywords: Sperm, DNA methylation, Retrotransposon, LINE, LTR, Gestational exposure, Arsenic
*Correspondence: [email protected] 1 Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba 305‑8506, Japan Full list of author information is available at the end of the article
Background Environment affects human health. Particularly, a fetus is vulnerable to such environmental impacts [1, 2]. The impacts on the fetus (F1) can induce long-term adverse effects after birth and are paternally and/or maternally inherited in their offspring (F2) and occasionally also in the subsequent generations in humans and model
© The Author(s) 2020. This article is licensed under a Creative Commons Attribution
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