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PRC1 and Suv39h specify parental asymmetry at constitutive heterochromatin in early mouse embryos

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Abstract

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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Figure 1: Maternal and paternal heterochromatin are marked by distinct repressive complexes in preimplantation embryos.
Figure 2: Differential heterochromatic states are maintained up to the 8-cell stage in a parental origin–dependent manner.
Figure 3: PRC1 components are targeted to chromatin upon gamete fusion.
Figure 4: Maternally provided Rnf2 is targeted to paternal constitutive heterochromatin and euchromatin.
Figure 5: Heterochromatic but not euchromatic matPRC1 targeting is Ezh2 independent.(a) Immunofluorescence analysis of germinal vesicle and M-II oocytes and PN0 zygotes shows that after gamete fusion (PN0), Ezh2 preferentially accumulates at the maternal genome complement that will constitute the embryo (bottom; arrow).
Figure 6: Parent of origin–specific labeling of constitutive heterochromatin and chromosome arms by Rnf2 and H3K9me3.
Figure 7: Absence of H3K9me3 and HP1β allows matPRC1 targeting to constitutive heterochromatin in early embryos.
Figure 8: MatPRC1 is required for transcriptional repression of major satellites on the paternal genome in early embryos.

Change history

  • 16 March 2008

    In the version of this article initially published online, the text in green associated with the right-most panel in Figure 1c should read ‘H3K27me3’, not ’H3K9me3’. The error has been corrected for all versions of the article.

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Acknowledgements

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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M.P. and A.H.F.M.P. conceived and designed the experiments. M.P., R.T., U.B. and C.K. performed the experiments. M.P., R.T., U.B. and A.H.F.M.P. analyzed the data. A.P.O. provided antibodies. E.B. and M.v.L. provided conditionally deficient Rnf2 mice. X.M. and S.H.O. provided conditionally deficient Ezh2 mice. K.I. and H.K. provided Rnf2–YFP knock-in mice. M.P. and A.H.F.M.P. wrote the manuscript.

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Correspondence to Antoine H F M Peters.

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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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