title: CHD1 acts via the Hmgpi pathway to regulate mouse early embryogenesis.
abstract: The protein CHD1 is a member of the family of ATPase-dependent chromatin remodeling factors. CHD1, which recognizes trimethylated histone H3 lysine 4, has been implicated in transcriptional activation in organisms ranging from yeast to humans. It is required for pre-mRNA maturation, maintenance of mouse embryonic stem cell pluripotency and rapid growth of the mouse epiblast. However, the function(s) of CHD1 in mouse preimplantation embryos has not yet been examined. Here, we show that loss of CHD1 function led to embryonic lethality after implantation. In mouse embryos in which Chd1 was targeted by siRNA microinjection, the expression of the key regulators of cell fate specification Pou5f1 (also known as Oct4), Nanog and Cdx2 was dramatically decreased, starting at mid-preimplantation gene activation (MGA). Moreover, expression of Hmgpi and Klf5, which regulate Pou5f1, Nanog and Cdx2, was also significantly suppressed at zygotic gene activation (ZGA). Suppression of Hmgpi expression in Chd1-knockdown embryos continued until the blastocyst stage, whereas suppression of Klf5 expression was relieved by the morula stage. Next, we rescued HMGPI expression via Hmgpi mRNA microinjection in Chd1-knockdown embryos. Consequently, Pou5f1, Nanog and Cdx2 expression was restored at MGA and live offspring were recovered. These findings indicate that CHD1 plays important roles in mouse early embryogenesis via activation of Hmgpi at ZGA.
authors.affiliation: Laboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Shinnosuke
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Laboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nozawa
authors.affiliation: Laboratory of Animal and Genome Sciences Section, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsukamoto
authors.affiliation: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Takehito
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Manabe
authors.affiliation: Laboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imai
authors.affiliation: Laboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan oog1nao@kais.kyoto-u.ac.jp.
authors.forename: Naojiro
authors.initials: N
authors.lastname: Minami
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D010064:Embryo Implantation / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D024002:HMGB Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008098:Litter Size; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015053:Zygote / Q000378:metabolism
chemical_list: C489844:Chd1 protein, mouse; D004268:DNA-Binding Proteins; D024002:HMGB Proteins; C548051:Hmgpi protein, mouse; D012333:RNA, Messenger
keywords: Chd1; Embryo development; Epigenetics; Mouse; Zygotic gene activation