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3 result(s) for "Funaya, Satoshi"
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Minor zygotic gene activation is essential for mouse preimplantation development
In mice, transcription initiates at the mid-one-cell stage and transcriptional activity dramatically increases during the two-cell stage, a process called zygotic gene activation (ZGA). Associated with ZGA is a marked change in the pattern of gene expression that occurs after the second round of DNA replication. To distinguish ZGA before and after the second-round DNA replication, the former and latter are called minor and major ZGA, respectively. Although major ZGA are required for development beyond the two-cell stage, the function of minor ZGA is not well understood. Transiently inhibiting minor ZGA with 5, 6-dichloro-1-β-D-ribofuranosyl-benzimidazole (DRB) resulted in the majority of embryos arresting at the two-cell stage and retention of the H3K4me3 mark that normally decreases. After release from DRB, at which time major ZGA normally occurred, transcription initiated with characteristics of minor ZGA but not major ZGA, although degradation of maternal mRNA normally occurred. Thus, ZGA occurs sequentially starting with minor ZGA that is critical for the maternal-to-zygotic transition.
Expression of Dux family genes in early preimplantation embryos
After fertilization, the zygotic genome is activated through two phases, minor zygotic activation (ZGA) and major ZGA. Recently, it was suggested that DUX is expressed during minor ZGA and activates some genes during major ZGA. However, it has not been proven that Dux is expressed during minor ZGA and functions to activate major ZGA genes, because there are several Dux paralogs that may be expressed in zygotes instead of Dux . In this study, we found that more than a dozen Dux paralogs, as well as Dux , are expressed during minor ZGA. Overexpression of some of these genes induced increased expression of major ZGA genes. These results suggest that multiple Dux paralogs are expressed to ensure a sufficient amount of functional Dux and its paralogs which are generated during a short period of minor ZGA with a low transcriptional activity. The mechanism by which multiple Dux paralogs are expressed is discussed.
Asymmetrical deposition and modification of histone H3 variants are essential for zygote development
The pericentromeric heterochromatin of one-cell embryos forms a unique, ring-like structure around the nucleolar precursor body, which is absent in somatic cells. Here, we found that the histone H3 variants H3.1 and/or H3.2 (H3.1/H3.2) were localized asymmetrically between the male and female perinucleolar regions of the one-cell embryos; moreover, asymmetrical histone localization influenced DNA replication timing. The nuclear deposition of H3.1/3.2 in one-cell embryos was low relative to other preimplantation stages because of reduced H3.1/3.2 mRNA expression and incorporation efficiency. The forced incorporation of H3.1/3.2 into the pronuclei of one-cell embryos triggered a delay in DNA replication, leading to developmental failure. Methylation of lysine residue 27 (H3K27me3) of the deposited H3.1/3.2 in the paternal perinucleolar region caused this delay in DNA replication. These results suggest that reduced H3.1/3.2 in the paternal perinucleolar region is essential for controlled DNA replication and preimplantation development. The nuclear deposition of H3.1/3.2 is presumably maintained at a low level to avoid the detrimental effect of K27me3 methylation on DNA replication in the paternal perinucleolar region.