WCRB2014 ORAL PRESENTATIONS Embryo (5 abstracts)
CHD1 is the zygotic determinant of Oct4 and Cdx2 expression via the Hmgpi pathway during preimplantation development
Shinnosuke Suzuki 1 , Yusuke Nozawa 1 , Satoshi Tsukamoto 2 , Takehito Kaneko 1 , Hiroshi Imai 1 & Naojiro Minami 1
1Kyoto University, Kyoto, Japan; 2National Institute of Radiological Sciences, Chiba, Japan.
Chromatin remodeling factor chromodomain helicase DNA binding protein 1 (CHD1) is a protein belonging to the family of ATPase dependent chromatin remodeling factors and recognizes tri-methylated lysine 4 of histone H3 (H3K4me3) in chromatin. Histone methylation is one of the epigenetic modifications involved in gene regulation and H3K4me3 is associated with a transcriptionally permissive state of chromatin. It has been shown that CHD1 facilitates pre-mRNA splicing, and is required for the maintenance of pluripotency in mouse ES cell via Oct4 activation. However, the role(s) of CHD1 in mouse preimplantation embryos has not yet been addressed (s1). In the present study, we investigated the expression pattern of Chd1 in mouse preimplantation embryos and the effects of RNA interference (RNAi)-mediated Chd1 repression on the development of mouse embryos. Here, we showed that Chd1 was zygotically expressed at the late two-cell stage and Chd1-knockdown at the two-cell stage led to early embryonic lethality due to the loss of ICM pluripotency. In Chd1-knockdown embryos, the levels of mRNAs and proteins of both Oct4 and Cdx2 were dramatically decreased. Furthermore, the mRNA and protein of Hmgpi which regulates the zygotic expression of Oct4 and Cdx2 were also significantly decreased. Based on the results, when HMGPI was rescued by microinjection of Hmgpi mRNA in Chd1-knockdown embryos, the levels of mRNAs and proteins of both Oct4 and Cdx2 and pluripotency of ICM cells were recovered. These results suggest that CHD1 has important roles in mouse embryonic development via the Hmgpi pathway.
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ISSN 2052-1472 (online)
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