Molecular determinants of nucleosome retention at CpG-rich sequences in mouse spermatozoa

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  • An Erratum to this article was published on 04 October 2013


In mammalian spermatozoa, most but not all of the genome is densely packaged by protamines. Here we reveal the molecular logic underlying the retention of nucleosomes in mouse spermatozoa, which contain only 1% residual histones. We observe high enrichment throughout the genome of nucleosomes at CpG-rich sequences that lack DNA methylation. Residual nucleosomes are largely composed of the histone H3.3 variant and are trimethylated at Lys4 of histone H3 (H3K4me3). Canonical H3.1 and H3.2 histones are also enriched at CpG-rich promoters marked by Polycomb-mediated H3K27me3, a modification predictive of gene repression in preimplantation embryos. Histone variant–specific nucleosome retention in sperm is strongly associated with nucleosome turnover in round spermatids. Our data show evolutionary conservation of the basic principles of nucleosome retention in mouse and human sperm, supporting a model of epigenetic inheritance by nucleosomes between generations.

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Figure 1: Nucleosome occupancy in sperm is highly dependent on CpG composition.
Figure 2: Nucleosome occupancy correlates negatively with DNA methylation in sperm.
Figure 3: Histone variant–specific packaging of sperm DNA.
Figure 4: CpG density and gene expression associate with nucleosome eviction in round spermatids.
Figure 5: Extent of nucleosome turnover in round spermatids relates to histone variant–specific retention in sperm.
Figure 6: Combinatorial effects of CpG density, histone variants and histone modifications underlie unique packaging of sperm DNA.
Figure 7: Model of nucleosome retention during spermiogenesis.

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  • 12 July 2013

    In the version of this article initially published, the parentheses in Figure 2a denoting noninclusive endpoints in ranges had not been indicated. The error has been corrected in the HTML and PDF versions of the article.


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We gratefully thank S. Dessus-Babus and T. Roloff (Friedrich Miescher Institute for Biomedical Research (FMI) functional genomics group), I. Nissen (Laboratory for Quantitative Genomics, D-BSSE, Basel), L. Burger (FMI bioinformatics group), H. Kohler (FMI FACS facility) and the FMI animal facility for excellent assistance. We thank members of the Peters laboratory for fruitful discussions. S.E. is supported as a recipient of a Boehringer Ingelheim Fond fellowship. M.G. and R.M. are supported by European Molecular Biology Organization (EMBO) Long Term fellowships (ALTF 253-2011 and ALTF 600-2008). Research in the Peters and Schübeler labs is supported by the Novartis Research Foundation and the Swiss Initiative in Systems Biology (Cell Plasticity, Systems Biology of Cell Differentiation). The Peters lab further acknowledges support from the Swiss National Science Foundation (31003A_125386 and National Research Programme NRP63, Stem Cells and Regenerative Medicine), the Japanese Swiss Science and Technology Cooperation Program, the FP7 Marie Curie Initial Training Network “Nucleosome4D” and the EMBO Young Investigator Program.

Author information

S.E., M.H. and A.H.F.M.P. conceived of and designed the experiments. S.E., M.H., C.-Y.L. and M.G. performed experiments. J.D. and J.v.d.V. provided antibodies. R.M. and D.S. performed and supervised bisulfite sequencing experiments, respectively. M.B.S. provided bioinformatics training and support. S.E., M.H., C.-Y.L., M.G., M.B.S. and A.H.F.M.P. analyzed the data. S.E. and A.H.F.M.P. prepared the manuscript.

Correspondence to Antoine H F M Peters.

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Erkek, S., Hisano, M., Liang, C. et al. Molecular determinants of nucleosome retention at CpG-rich sequences in mouse spermatozoa. Nat Struct Mol Biol 20, 868–875 (2013) doi:10.1038/nsmb.2599

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