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Distinctive chromatin in human sperm packages genes for embryo development

Author

Listed:
  • Saher Sue Hammoud

    (Howard Hughes Medical Institute, and Huntsman Cancer Institute
    IVF and Andrology Laboratories, Obstetrics and Gynecology, and Physiology)

  • David A. Nix

    (Research Informatics and Bioinformatics Core Facility, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA)

  • Haiying Zhang

    (Howard Hughes Medical Institute, and Huntsman Cancer Institute)

  • Jahnvi Purwar

    (Howard Hughes Medical Institute, and Huntsman Cancer Institute)

  • Douglas T. Carrell

    (IVF and Andrology Laboratories, Obstetrics and Gynecology, and Physiology)

  • Bradley R. Cairns

    (Howard Hughes Medical Institute, and Huntsman Cancer Institute)

Abstract

Because nucleosomes are widely replaced by protamine in mature human sperm, the epigenetic contributions of sperm chromatin to embryo development have been considered highly limited. Here we show that the retained nucleosomes are significantly enriched at loci of developmental importance, including imprinted gene clusters, microRNA clusters, HOX gene clusters, and the promoters of stand-alone developmental transcription and signalling factors. Notably, histone modifications localize to particular developmental loci. Dimethylated lysine 4 on histone H3 (H3K4me2) is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX clusters, certain noncoding RNAs, and generally to paternally expressed imprinted loci, but not paternally repressed loci. Notably, trimethylated H3K27 (H3K27me3) is significantly enriched at developmental promoters that are repressed in early embryos, including many bivalent (H3K4me3/H3K27me3) promoters in embryonic stem cells. Furthermore, developmental promoters are generally DNA hypomethylated in sperm, but acquire methylation during differentiation. Taken together, epigenetic marking in sperm is extensive, and correlated with developmental regulators.

Suggested Citation

  • Saher Sue Hammoud & David A. Nix & Haiying Zhang & Jahnvi Purwar & Douglas T. Carrell & Bradley R. Cairns, 2009. "Distinctive chromatin in human sperm packages genes for embryo development," Nature, Nature, vol. 460(7254), pages 473-478, July.
  • Handle: RePEc:nat:nature:v:460:y:2009:i:7254:d:10.1038_nature08162
    DOI: 10.1038/nature08162
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    Cited by:

    1. Xuedi Zhang & Ju Peng & Menghua Wu & Angyang Sun & Xiangyu Wu & Jie Zheng & Wangfei Shi & Guanjun Gao, 2023. "Broad phosphorylation mediated by testis-specific serine/threonine kinases contributes to spermiogenesis and male fertility," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Ariane Lismer & Sarah Kimmins, 2023. "Emerging evidence that the mammalian sperm epigenome serves as a template for embryo development," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    3. Pasquale Perrone & Gennaro Lettieri & Carmela Marinaro & Valentina Longo & Simonetta Capone & Angiola Forleo & Sebastiana Pappalardo & Luigi Montano & Marina Piscopo, 2022. "Molecular Alterations and Severe Abnormalities in Spermatozoa of Young Men Living in the “Valley of Sacco River” (Latium, Italy): A Preliminary Study," IJERPH, MDPI, vol. 19(17), pages 1-18, September.
    4. Filomena Mazzeo & Rosaria Meccariello, 2023. "Cannabis and Paternal Epigenetic Inheritance," IJERPH, MDPI, vol. 20(9), pages 1-14, April.
    5. Carlos Olmeda-Gómez & Carlos Romá-Mateo & Maria-Antonia Ovalle-Perandones, 2019. "Overview of trends in global epigenetic research (2009–2017)," Scientometrics, Springer;Akadémiai Kiadó, vol. 119(3), pages 1545-1574, June.

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