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H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos

Maintaining genomic integrity in mammalian early embryos, which are deficient in DNA damage repair, is critical for normal preimplantation and subsequent development. Abnormalities in DNA damage repair in preimplantation embryos can cause not only developmental arrest, but also diseases such as cong...

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Autores principales: SHIKATA, Daiki, YAMAMOTO, Takuto, HONDA, Shinnosuke, IKEDA, Shuntaro, MINAMI, Naojiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Society for Reproduction and Development 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593633/
https://www.ncbi.nlm.nih.gov/pubmed/32378528
http://dx.doi.org/10.1262/jrd.2020-036
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author SHIKATA, Daiki
YAMAMOTO, Takuto
HONDA, Shinnosuke
IKEDA, Shuntaro
MINAMI, Naojiro
author_facet SHIKATA, Daiki
YAMAMOTO, Takuto
HONDA, Shinnosuke
IKEDA, Shuntaro
MINAMI, Naojiro
author_sort SHIKATA, Daiki
collection PubMed
description Maintaining genomic integrity in mammalian early embryos, which are deficient in DNA damage repair, is critical for normal preimplantation and subsequent development. Abnormalities in DNA damage repair in preimplantation embryos can cause not only developmental arrest, but also diseases such as congenital disorders and cancers. Histone H4 lysine 20 monomethylation (H4K20me1) is involved in DNA damage repair and regulation of gene expression. However, little is known about the role of H4K20me1 during mouse preimplantation development. In this study, we revealed that H4K20me1 mediated by SETD8 is involved in maintaining genomic integrity. H4K20me1 was present throughout preimplantation development. In addition, reduction in the level of H4K20me1 by inhibition of SETD8 activity or a dominant-negative mutant of histone H4 resulted in developmental arrest at the S/G2 phase and excessive accumulation of DNA double-strand breaks. Together, our results suggest that H4K20me1, a type of epigenetic modification, is associated with the maintenance of genomic integrity and is essential for preimplantation development. A better understanding of the mechanisms involved in maintaining genome integrity during preimplantation development could contribute to advances in reproductive medicine and technology.
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spelling pubmed-75936332020-11-03 H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos SHIKATA, Daiki YAMAMOTO, Takuto HONDA, Shinnosuke IKEDA, Shuntaro MINAMI, Naojiro J Reprod Dev Original Article Maintaining genomic integrity in mammalian early embryos, which are deficient in DNA damage repair, is critical for normal preimplantation and subsequent development. Abnormalities in DNA damage repair in preimplantation embryos can cause not only developmental arrest, but also diseases such as congenital disorders and cancers. Histone H4 lysine 20 monomethylation (H4K20me1) is involved in DNA damage repair and regulation of gene expression. However, little is known about the role of H4K20me1 during mouse preimplantation development. In this study, we revealed that H4K20me1 mediated by SETD8 is involved in maintaining genomic integrity. H4K20me1 was present throughout preimplantation development. In addition, reduction in the level of H4K20me1 by inhibition of SETD8 activity or a dominant-negative mutant of histone H4 resulted in developmental arrest at the S/G2 phase and excessive accumulation of DNA double-strand breaks. Together, our results suggest that H4K20me1, a type of epigenetic modification, is associated with the maintenance of genomic integrity and is essential for preimplantation development. A better understanding of the mechanisms involved in maintaining genome integrity during preimplantation development could contribute to advances in reproductive medicine and technology. The Society for Reproduction and Development 2020-05-06 2020-10 /pmc/articles/PMC7593633/ /pubmed/32378528 http://dx.doi.org/10.1262/jrd.2020-036 Text en ©2020 Society for Reproduction and Development This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Original Article
SHIKATA, Daiki
YAMAMOTO, Takuto
HONDA, Shinnosuke
IKEDA, Shuntaro
MINAMI, Naojiro
H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos
title H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos
title_full H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos
title_fullStr H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos
title_full_unstemmed H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos
title_short H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos
title_sort h4k20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593633/
https://www.ncbi.nlm.nih.gov/pubmed/32378528
http://dx.doi.org/10.1262/jrd.2020-036
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