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PGC7/Stella protects against DNA demethylation in early embryogenesis

Abstract

DNA methylation is an important means of epigenetic gene regulation1,2 and must be carefully controlled as a prerequisite for normal early embryogenesis. Although global demethylation occurs soon after fertilization, it is not evenly distributed throughout the genome. Genomic imprinting and epigenetic asymmetry between parental genomes, that is, delayed demethylation of the maternal genome after fertilization3,4,5,6, are clear examples of the functional importance of DNA methylation. Here, we show that PGC7/Stella, a maternal factor essential for early development, protects the DNA methylation state of several imprinted loci and epigenetic asymmetry. After determining that PGC7/Stella binds to Ran binding protein 5 (RanBP5; a nuclear transport shuttle protein), mutant versions of the two proteins were used to examine exactly when and where PGC7/Stella functions within the cell. It is likely that PGC7/Stella protects the maternal genome from demethylation only after localizing to the nucleus, where it maintains the methylation of several imprinted genes. These results demonstrate that PGC7/Stella is indispensable for the maintenance of methylation involved in epigenetic reprogramming after fertilization.

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Figure 1: Identification of PGC7/Stella binding proteins.
Figure 2: Control of PGC7/Stella subcellular localization.
Figure 3: Nuclear localization of PGC7/Stella during early embryogenesis.
Figure 4: Early demethylation of the maternal genome in zygotes lacking PGC7/Stella.
Figure 5: Methylation status of various genes in early embryogenesis.

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Acknowledgements

We thank M. Sato for an initial contribution to this study, and. H. Niwa, K. Nakayama and T. A. Van Dyke for providing plasmids. We also thank Y. Fujita, M. Ikeuchi and N. Asada for assistance, and A. Mizokami for secretarial assistance. This work was supported in part by grants from the Ministry of Education, Science, Sports, Culture, and Technology; the Support Program for Technology Development on the Basis of Academic Findings (NEDO); the Uehara Memorial Foundation; the Osaka Cancer Foundation; and the 21st Century COE “CICET”.

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Correspondence to Toru Nakano.

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Nakamura, T., Arai, Y., Umehara, H. et al. PGC7/Stella protects against DNA demethylation in early embryogenesis. Nat Cell Biol 9, 64–71 (2007). https://doi.org/10.1038/ncb1519

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