Function Study Of Wdr82 Protein In Mouse Early Embryo Development

Epigenetic regulation is considered one of the most important mechanisms by which to make changes in gene expression other than changes in the underlying DNA sequence. More and more studies have shown that this kind of regulation plays a very important role during the process of early embryo development. Methylation of histones is a special type of epigenetic regulation that plays a dual role; tri-methylation of histone 3 lysine 4 has been shown to be a marker of gene expression activation.Previous studies have proved that the loss of tri-methylation on histone 3 lysine 4 could result in inhibition of cell growth in yeast and human cell lines. And in mammalian the defect of methyltransferases of histone 3 lysine 4 had fatal or carcinogenicity on living beings. The loss of Wdr82 protein in human cell line caused significantly decrease of tri-methylation on histone 3 lysine 4. In previous study proceeded in our lab, Wdr82 protein was recognized in the proteomic map of MII oocyte. And other study has proved that Wdr82 protein expressed in embryo stem cells both undifferentiation and differentiation and show amount decrease after stem cells undergone differentiation.The above results led us focusd on Wdr82 protein; it had been proved that Wdr82 protein played as a subunit of one kind of methyltransferase responsible for tri-methylation on histone 3 lysine 4 during the process of early embryo development. But the exact role of Wdr82 in the methyltransferases complex during early embryo development is still not clear. Our study showed that the expression level of Wdr82 protein increased in zygote compared with in MII oocyte and localized in nuclei in early embryos.Through the microinjection of siRNA and antibody, Wdr82 protein function was blocked in mRNA level or protein level in early embryos. Our results showed that during the process of early embryo development, the defect of Wdr82 would cause seriously redartation of development and was lethial to embryo, which then caused no live pups to birth. Further study showed this kind of development retardation and embryo fatal was associated with the dysfunction of methyltransferases complex Set1A/B, which affected the normal embryo development through the regulation on target genes expression. In our study, Oct-4 was recognized as a downstream factor of Set1A/B, the defect of Wdr82 protein could cause downregulated expression of Oct-4 and finally caused the development retardation and embryo fatal.In summary, our study proved the key function of Wdr82 protein in mouse early embryo development. During the process of early embryo development, Wdr82 protein acted as a regulator of embryo development associated key factors, activated the transcription of these factors in time to make sure the normal embryo development and survive.