DNA methylation is one of the important modifications in epigenetic gene regulation, and the control of DNA methylation status is a prerequisite for normal early embryogenesis and cell differentiation. We have been analyzing two proteins, PGC7/Stella and MILI, which play crucial roles in the DNA methylation in early embryogenesis and spermatogenesis, respectively.Although global demethylation occurs soon after fertilization, demethylation does not take place on the whole genome evenly. Maintenance of the methylation in the imprinted genes and epigenetic asymmetry between parental genomes, i.e., delayed demethylation of the maternal genome after fertilization are good examples of the protection of DNA methylation status. As one of the topics, I will show that PGC7/Stella, a maternal factor essential for early development, plays some roles in the protection of the DNA methylation in several genomic imprinting loci and epigenetic asymmetry. After determining that PGC7/ Stella binds to Ran binding protein 5 (RanBP5), a nuclear shuttle transporter protein, we examined the exact time when, and subcellular location where, PGC7/Stella functions, using mutants of PGC7/Stella and RanBP5. PGC7/ Stella turn out to be implicated in protecting the maternal genome from demethylation only after localization to the nucleus and maintaining the methylation of several imprinted genes. These results demonstrate that PGC7/Stella is an indispensable methylation protector involved in epigenetic reprogramming after fertilization.The other topic I will introduce is the function of small RNA in gene silencing. Gene silencing in mammals is believed to be controlled by RNA interference in the same way as in other organisms; however, the molecules involved in the process remain unclear. The Argonaut proteins which include Piwi family proteins, are the candidates for controlling the silencing process. We have shown that a member of mouse Piwi family, MILI, plays crucial roles in the piRNA class of small RNA processing and/or protection, and subsequent gene silencing of retrotransposons through de novo DNA methylation at early spermatogenesis