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Sperm is epigenetically programmed to regulate gene transcription in embryos.

Published version
Peer-reviewed

Repository DOI


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Authors

Simeone, Angela 
Miyamoto, Kei 
Allen, George E 

Abstract

For a long time, it has been assumed that the only role of sperm at fertilization is to introduce the male genome into the egg. Recently, ideas have emerged that the epigenetic state of the sperm nucleus could influence transcription in the embryo. However, conflicting reports have challenged the existence of epigenetic marks on sperm genes, and there are no functional tests supporting the role of sperm epigenetic marking on embryonic gene expression. Here, we show that sperm is epigenetically programmed to regulate embryonic gene expression. By comparing the development of sperm- and spermatid-derived frog embryos, we show that the programming of sperm for successful development relates to its ability to regulate transcription of a set of developmentally important genes. During spermatid maturation into sperm, these genes lose H3K4me2/3 and retain H3K27me3 marks. Experimental removal of these epigenetic marks at fertilization de-regulates gene expression in the resulting embryos in a paternal chromatin-dependent manner. This demonstrates that epigenetic instructions delivered by the sperm at fertilization are required for correct regulation of gene expression in the future embryos. The epigenetic mechanisms of developmental programming revealed here are likely to relate to the mechanisms involved in transgenerational transmission of acquired traits. Understanding how parental experience can influence development of the progeny has broad potential for improving human health.

Description

Keywords

Animals, DNA Methylation, Embryonic Development, Epigenesis, Genetic, Gene Expression Regulation, Developmental, Histone-Lysine N-Methyltransferase, Histones, Humans, Male, Ranidae, Spermatids, Spermatozoa

Journal Title

Genome Res

Conference Name

Journal ISSN

1088-9051
1549-5469

Volume Title

26

Publisher

Cold Spring Harbor Laboratory
Sponsorship
Medical Research Council (MR/K011022/1)
Worldwide Cancer Research (formerly AICR) (10-0908)
Medical Research Council (G1001690)
Wellcome Trust (101050/Z/13/Z)
Medical Research Council (MR/P000479/1)
Wellcome Trust (092096/Z/10/Z)
Wellcome Trust (089613/Z/09/Z)
Cancer Research Uk (None)
Wellcome Trust (107056/Z/15/Z)
We thank: T. Jenuwein and N. Shukeir for anti-H3K27me3 antibody; A. Bannister, J. Ahringer and E. Miska for comments on the manuscript; Gurdon group members for reading the manuscript; The International Xenopus laevis Genome Project Consortium (the Harland, Rokhsar, Taira labs and others) for providing unpublished genome and gene annotation information. M.T. is supported by WT089613 and by MR/K011022/1. V.G. and P.Z. are funded by AICR 10-0908. A.S. is supported by MR/K011022/1. K.M. is a Research Fellow at Wolfson College and is supported by the Herchel Smith Postdoctoral Fellowship. E.M.M. is supported by National Institutes of Health, National Science Foundation, Cancer Prevention Research Institute of Texas, and the Welch Foundation (F1515). J.J. and J.B.G. are supported by WT101050/Z/13/Z. S.E. acknowledges Boehringer Ingelheim Fond fellowship. A.H.F.M.P. is supported by the Swiss National Science Foundation (31003A_125386) and the Novartis Research Foundation. All members of the Gurdon Institute acknowledge the core support provided by CRUK C6946/A14492 and WT092096.