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Gestational arsenic exposure induces site-specific DNA hypomethylation in active retrotransposon subfamilies in offspring sperm in mice

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 ges...

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Autores principales: Nohara, Keiko, Nakabayashi, Kazuhiko, Okamura, Kazuyuki, Suzuki, Takehiro, Suzuki, Shigekatsu, Hata, Kenichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709384/
https://www.ncbi.nlm.nih.gov/pubmed/33267854
http://dx.doi.org/10.1186/s13072-020-00375-3
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author Nohara, Keiko
Nakabayashi, Kazuhiko
Okamura, Kazuyuki
Suzuki, Takehiro
Suzuki, Shigekatsu
Hata, Kenichiro
author_facet Nohara, Keiko
Nakabayashi, Kazuhiko
Okamura, Kazuyuki
Suzuki, Takehiro
Suzuki, Shigekatsu
Hata, Kenichiro
author_sort Nohara, Keiko
collection PubMed
description 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.
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spelling pubmed-77093842020-12-03 Gestational arsenic exposure induces site-specific DNA hypomethylation in active retrotransposon subfamilies in offspring sperm in mice Nohara, Keiko Nakabayashi, Kazuhiko Okamura, Kazuyuki Suzuki, Takehiro Suzuki, Shigekatsu Hata, Kenichiro Epigenetics Chromatin Research 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. BioMed Central 2020-12-02 /pmc/articles/PMC7709384/ /pubmed/33267854 http://dx.doi.org/10.1186/s13072-020-00375-3 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Nohara, Keiko
Nakabayashi, Kazuhiko
Okamura, Kazuyuki
Suzuki, Takehiro
Suzuki, Shigekatsu
Hata, Kenichiro
Gestational arsenic exposure induces site-specific DNA hypomethylation in active retrotransposon subfamilies in offspring sperm in mice
title Gestational arsenic exposure induces site-specific DNA hypomethylation in active retrotransposon subfamilies in offspring sperm in mice
title_full Gestational arsenic exposure induces site-specific DNA hypomethylation in active retrotransposon subfamilies in offspring sperm in mice
title_fullStr Gestational arsenic exposure induces site-specific DNA hypomethylation in active retrotransposon subfamilies in offspring sperm in mice
title_full_unstemmed Gestational arsenic exposure induces site-specific DNA hypomethylation in active retrotransposon subfamilies in offspring sperm in mice
title_short Gestational arsenic exposure induces site-specific DNA hypomethylation in active retrotransposon subfamilies in offspring sperm in mice
title_sort gestational arsenic exposure induces site-specific dna hypomethylation in active retrotransposon subfamilies in offspring sperm in mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709384/
https://www.ncbi.nlm.nih.gov/pubmed/33267854
http://dx.doi.org/10.1186/s13072-020-00375-3
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