PGC7/Stella protects against DNA demethylation in early embryogenesis
| Autor: | Kunio Shiota, Tohru Kimura, Yoshikazu Arai, Masahito Ikawa, Hisaaki Taniguchi, Yoshihiro Yoneda, Toshinobu Nakamura, Hiroki Umehara, Masaru Okabe, Satoshi Tanaka, Masaaki Masuhara, Toru Nakano, Toshihiro Sekimoto |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Chromosomal Proteins Non-Histone Embryonic Development Biology Transfection Cell Line Epigenesis Genetic Mice Chlorocebus aethiops Animals Humans Epigenetics RNA-Directed DNA Methylation Cell Nucleus Regulation of gene expression Genetics Gene Expression Regulation Developmental Proteins Cell Biology Methylation DNA Methylation Cell biology DNA demethylation Fertilization COS Cells DNA methylation Female Genomic imprinting Reprogramming |
| Zdroj: | Nature Cell Biology. 9:64-71 |
| ISSN: | 1476-4679 1465-7392 |
| DOI: | 10.1038/ncb1519 |
| Popis: | DNA methylation is an important means of epigenetic gene regulation 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 fertilization, 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. |
| Databáze: | OpenAIRE |
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