Epigenetic Regulation in Development and Differentiation

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Establishment of epigenetic state is critically important for development and differentiation of multicellular organisms. In this project, we carried out following three issues on the establishment of epigenetic status.1. Function of PGC7/ Stella, a regulator of DNA methylation in early embryos.: PGC7/ Stella has the effect to prevent" active DNA demethylation" in early embryos. We identified that the binding of PGC/ Stella to H3K9me2(dimethylated lysine 9 of histone H3) is critically important for the function. During the course of this project, Tet protein plays critical roles in active DNA demethylation by converting 5-methyl cytosine to 5-hydroxymethyl cytosine. Based on this data, we revealed that the binding of Tet-3, the most abundant Tet protein in early embryos, to chromatin is inhibited by PGC7.2. We analyzed the function of GATA-1 transcription factor using in vitro hematopoietic differentiation induction system from ES cells. Controlled expression of GATA-1 at different time points showed that the function of the factor is quite varied dependent on the time point and its different roles were controlled by epigenetic mechanisms.3. We find that GS cells(Germline stem cells) are a quite useful resource for studying the biogenesis of piRNA and that the initial phase of piRNA production is carried out in the cells. Using GS cells, we succeeded to identify a protein involved in piRNA biogenesis. In addition, we established a novel experimental system to induce piRNA and subsequent DNA methylation in the transgenic mice.