In higher eukaryotes, histone methylation is involved in maintaining cellular identity during somatic development. As most nucleosomes are replaced by protamines during spermatogenesis, it is unclear whether histone modifications function in paternal transmission of epigenetic information. Here we show that two modifications important for Trithorax- and Polycomb-mediated gene regulation have methylation-specific distributions at regulatory regions in human spermatozoa. Histone H3 Lys4 dimethylation (H3K4me2) marks genes that are relevant in spermatogenesis and cellular homeostasis. In contrast, histone H3 Lys27 trimethylation (H3K27me3) marks developmental regulators in sperm, as in somatic cells. However, nucleosomes are only moderately retained at regulatory regions in human sperm. Nonetheless, genes with extensive H3K27me3 coverage around transcriptional start sites in particular tend not to be expressed during male and female gametogenesis or in preimplantation embryos. Promoters of orthologous genes are similarly modified in mouse spermatozoa. These data are compatible with a role for Polycomb in repressing somatic determinants across generations, potentially in a variegating manner.
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We thank T. Jenuwein (Max-Planck Institute of Immunobiology, Freiburg, Germany) and R. Foisner (Max F. Perutz Laboratories, Medical University of Vienna, Vienna, Austria) for providing antisera. We are grateful to F. Zilbermann and the Friedrich Miescher Institute (FMI) animal facility for excellent technical assistance. We thank P. de Boer and R. Terranova for critical reading of the manuscript and all members of the Peters and Schübeler laboratories for discussions. U.B. and S.E. acknowledge the Boehringer Ingelheim Fonds for their PhD fellowships. M.H. was supported by the Swiss National Science Foundation and the Japan Society for the Promotion of Science. T.C.R. was supported by the Swiss Cancer Leagues. Research in the Peters laboratory is supported by the Novartis Research Foundation, the Swiss National Science Foundation, the European Network of Excellence “The Epigenome” and the EMBO YIP program.
The authors declare no competing financial interests.
Supplementary Figures 1–8 and Supplementary Methods (PDF 2592 kb)
List of genes with modification states in human spermatozoa (XLS 3667 kb)
List of significantly over- and under-represented GO terms for Fig. 1d, 3d, 3e (XLS 842 kb)
Real-time PCR primer sequences (XLS 38 kb)
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Brykczynska, U., Hisano, M., Erkek, S. et al. Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat Struct Mol Biol 17, 679–687 (2010). https://doi.org/10.1038/nsmb.1821
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