Letter abstract
Nature Cell Biology 9, 64 - 71 (2006)
Published online: 3 December 2006 | doi:10.1038/ncb1519
PGC7/Stella protects against DNA demethylation in early embryogenesis
Toshinobu Nakamura1, Yoshikazu Arai2, Hiroki Umehara1, Masaaki Masuhara3, Tohru Kimura1, Hisaaki Taniguchi4, Toshihiro Sekimoto5, Masahito Ikawa6, Yoshihiro Yoneda7, Masaru Okabe6,8, Satoshi Tanaka2, Kunio Shiota2 & Toru Nakano1
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.
- Department of Pathology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
- Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
- Department of Oral Anatomy, Meikai University School of Dentistry, Saitama 350-0283 Japan.
- Institute for Enzyme Research, The University of Tokushima, Tokushima 770-8503, Japan.
- Department of Cell Biology and Neuroscience, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
- Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
- Department of Frontier Biosciences, Graduate School of Frontier Bioscience; Osaka University, Osaka 565-0871, Japan.
- Genome Information Research Center, Osaka University, Osaka 565-0871, Japan.
Correspondence to: Toru Nakano1 e-mail: tnakano@patho.med.osaka-u.ac.jp
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