Polycomb function during oogenesis is required for mouse embryonic development

Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel, Switzerland.
Genes & development (Impact Factor: 10.8). 04/2012; 26(9):920-32. DOI: 10.1101/gad.188094.112
Source: PubMed

ABSTRACT In mammals, totipotent embryos are formed by fusion of highly differentiated gametes. Acquisition of totipotency concurs with chromatin remodeling of parental genomes, changes in the maternal transcriptome and proteome, and zygotic genome activation (ZGA). The inefficiency of reprogramming somatic nuclei in reproductive cloning suggests that intergenerational inheritance of germline chromatin contributes to developmental proficiency after natural conception. Here we show that Ring1 and Rnf2, components of Polycomb-repressive complex 1 (PRC1), serve redundant transcriptional functions during oogenesis that are essential for proper ZGA, replication and cell cycle progression in early embryos, and development beyond the two-cell stage. Exchange of chromosomes between control and Ring1/Rnf2-deficient metaphase II oocytes reveal cytoplasmic and chromosome-based contributions by PRC1 to embryonic development. Our results strongly support a model in which Polycomb acts in the female germline to establish developmental competence for the following generation by silencing differentiation-inducing genes and defining appropriate chromatin states.

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Available from: Antoine H F M Peters, Sep 28, 2015
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    • "Similarly, inhibition of H3K4 demethylation by " bisguanidine 1c " resulted in aberrant expression of Oct4 by the 2-cell stage and inhibited the second embryonic cleavage to 4-cell (Shao et al., 2008). Recently, we also showed that components of the PRC1 complex, that binds H3K27me3, serve transcriptional functions during oogenesis that are essential for proper EGA and developmental progression beyond the two-cell stage (Posfai et al., 2012). Altogether these results suggest that histone acetylation and methylation may be closely correlated with the formation of a transcriptionally active or repressive state respectively during EGA and that they participate in the establishment of appropriate gene expression patterns required for further development. "
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    ABSTRACT: In mammals, epigenetic modifications are globally rearranged after fertilization, when gametes fuse to form the embryo. While gametes carry special epigenetic signatures and a unique nuclear organization, they attain embryo-specific patterns after fertilization. This "reprogramming" is promoted by intimate contact between the parental inherited genomes and the oocyte cytoplasm over the first cell cycles of development. Although the mechanisms of this reprogramming remain poorly understood, it appears that the particular epigenetic landscape established after fertilization is essential for further development. This review looks at histone post-translational modifications, focusing on their functions in chromatin organization and their role in nuclear architecture during mouse embryonic development. I also consider epigenetic changes linked to the use of assisted reproductive technologies. Mol. Reprod. Dev. © 2013 Wiley Periodicals, Inc.
    Molecular Reproduction and Development 02/2014; 81(2). DOI:10.1002/mrd.22268 · 2.53 Impact Factor
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    • "Perturbation of Ring1a or Ring1b in mice causes axial skeletal transformations (del Mar Lorente et al., 2000; Suzuki et al., 2002) due to defects in Hox gene expression, while deletion of Ring1b alone or both Ring1a and Ring1b leads to embryonic lethality (Posfai et al., 2012; Voncken et al., 2003). To understand how PCGF1/PRC1 targeting affects development, mice hemizygous for loss of the KDM2B ZF-CxxC domain were generated by crossing Kdm2b fl/fl mice to a mouse constitutively expressing Cre-recombinase. "
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    • "Whereas Porcn transcript is detectable at increasing levels from the 2-cell to the morula stage and at low levels in blastocysts (Casanova et al., 2012; Hamatani et al., 2004; Xie et al., 2010), it is undetectable in oocytes (Macfarlan et al., 2012; Posfai et al., 2012), suggesting that rescue by maternal protein is unlikely to explain the absence of any early embryo defects in Porcn zygotic mutants. In order to test this more directly, we generated Porcn lox/lox ; Zp3- Cre +/tg females that delete Porcn in the developing oocytes (Lewandoski et al., 1997) and crossed them to wild-type males carrying an X-linked EGFP transgene (Hadjantonakis et al., 1998). "
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    ABSTRACT: In mice and humans the X-chromosomal porcupine homolog (Porcn) gene is required for the acylation and secretion of all 19 Wnt ligands and thus represents a bottleneck for all Wnt signaling. We have generated a mouse line carrying a floxed allele for Porcn and used zygotic, oocyte-specific and visceral endoderm-specific deletions to investigate embryonic and extra-embryonic requirements for Wnt ligand secretion. We show that there is no requirement for Porcn-dependent secretion of Wnt ligands during preimplantation development of the mouse embryo. Porcn-dependent Wnts are first required for the initiation of gastrulation, where Porcn function is required in the epiblast but not the visceral endoderm. Heterozygous female embryos, which are mutant in both trophoblast and visceral endoderm due to imprinted X chromosome inactivation, complete gastrulation but display chorio-allantoic fusion defects similar to Wnt7b mutants. Our studies highlight the importance of Wnt3 and Wnt7b for embryonic and placental development but suggest that endogenous Porcn-dependent Wnt secretion does not play an essential role in either implantation or blastocyst lineage specification.
    Development 06/2013; 140(14). DOI:10.1242/dev.094458 · 6.46 Impact Factor
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