Overlapping peri-implantation phenotypes of ZNHIT1 and ZNHIT2 despite distinct functions during early mouse development.
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ABSTRACT:
PROVIDER: PRJNA1157720 | ENA |
REPOSITORIES: ENA
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Project description:Mammalian preimplantation development culminates in the formation of a blastocyst which undergoes extensive gene expression regulation to successfully implant into the maternal endometrium. Zinc-finger HIT domain-containing (ZNHIT) 1 and 2 are members of a highly conserved family, yet they have been identified as subunits of distinct complexes. Here we report that knockout of either Znhit1 or Znhit2 results in embryonic lethality during peri-implantation stages. Znhit1 and Znhit2 mutant embryos have overlapping phenotypes, including reduced proportion of SOX2-positive ICM cells, a lack of Fgf4 expression and aberrant expression of NANOG and SOX17. Furthermore, we find that the similar phenotypes are caused by distinct mechanisms. Specifically, embryos lacking ZNHIT1 likely fail to incorporate sufficient H2A.Z at the promoter region of Fgf4 and other genes involved in cell projection organization resulting in impaired invasion of trophoblast cells during implantation. In contrast, Znhit2 mutant embryos display a complete lack of nuclear EFTUD2, a key component of U5 spliceosome, indicating a global splicing deficiency. Our findings unveil the indispensable yet distinct roles of ZNHIT1 and ZNHIT2 in early mammalian embryonic development.
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Project description:A novel porcine cDNA microarray, containing PCR products selected for embryonic expression, was used for transcriptional profiling during conceptus development. Total RNA from quadruplicate samples of small spherical (1-5mm), large spherical (6-11mm), tubular (13-45mm), and filamentous (>100mm) was extracted, amplified, and converted to 32P labeled target and hybridized to membranes. Porcine peri-implantation embryo development order is from small spherical to large spherical, then to Tubular, then to filamentous. All this morphological transmission is within two days (day 10 to day 12). In this study, we investigated the gene expression changes by a specifically selected porcine embryo gene array. A number of genes were found to be differentially expressed during those developmental stages and confirmed by quantitative PCR. Keywords = Gene expression Keywords = porcine conceptus Keywords = cDNA microarray Keywords = peri-implantation Keywords = transcriptional profiling Keywords: time-course
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