In eukaryotes, Suv39h H3K9 trimethyltransferases are required for pericentric heterochromatin formation and function. In early mouse preimplantation embryos, however, paternal pericentric heterochromatin lacks Suv39h-mediated H3K9me3 and downstream marks. Here we demonstrate Ezh2-independent targeting of maternally provided polycomb repressive complex 1 (PRC1) components to paternal heterochromatin. In Suv39h2 maternally deficient zygotes, PRC1 also associates with maternal heterochromatin lacking H3K9me3, thereby revealing hierarchy between repressive pathways. In Rnf2 maternally deficient zygotes, the PRC1 complex is disrupted, and levels of pericentric major satellite transcripts are increased at the paternal but not the maternal genome. We conclude that in early embryos, Suv39h-mediated H3K9me3 constitutes the dominant maternal transgenerational signal for pericentric heterochromatin formation. In absence of this signal, PRC1 functions as the default repressive back-up mechanism. Parental epigenetic asymmetry, also observed along cleavage chromosomes, is resolved by the end of the 8-cell stage—concurrent with blastomere polarization—marking the end of the maternal-to-embryonic transition.
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We thank M. Vidal (Centro de Investigaciones Biológicas, Spain) and T. Jenuwein (Research Institute of Molecular Pathology, Austria) for providing antisera. Moreover, we are grateful to T. Jenuwein and B. Knowles (The Jackson Laboratory, USA) for providing Suv39h2 deficient and Zp3-cre transgenic mice, respectively. We acknowledge excellent assistance by Friedrich Miescher Institute (FMI) colleagues P. Schwarb and J. Rietdorf (microscopy and imaging facility), B. Heller-Stilb and J.-F. Spetz (animal facility), S. Bichet (histology) and M. Stadler (bioinformatics). We thank members of the Peters laboratory for fruitful discussions and P. de Boer, D. Schübeler, S. Gasser and P. Hublitz for valuable comments on the manuscript. Research at the Friedrich Miescher Institute is supported by the Novartis Research Foundation. M.P. acknowledges the Boehringer Ingelheim Fonds for her PhD fellowship. Research in the Peters laboratory is supported by the EU NoE network 'The Epigenome' (LSHG-CT-2004-503433).
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Puschendorf, M., Terranova, R., Boutsma, E. et al. PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos. Nat Genet 40, 411–420 (2008). https://doi.org/10.1038/ng.99
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