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- W4386640467 abstract "ZNF554 is highly expressed in the placenta and regulates trophoblastic functions, including deep invasion into maternal tissues, a unique feature in humans that is inhibited in preeclampsia. Here, we investigated how the evolution of the ZNF554 locus affected the regulation of placental ZNF554 expression, trophoblast invasion, and the vulnerability to preeclampsia. The evolution of the ZNF554 locus was examined in silico using the USCS Genome Brower. The transcriptional regulation of ZNF554 by ZEB1, ZEB2, and hypoxia was investigated in vitro by luciferase assay. We investigated the neighboring hypoxia-response elements (HREs) located in AluY and their hypermethylation in preeclampsia. For this, we analyzed three CpG deletion clones by luciferase assay. The evolution of the ZNF554 locus in primates involved the insertion of primate-specific transposable elements into the 5' flanking region, which established ZEB binding sites and HREs. In humans, LTR10A elements were multiplicated, which introduced numerous ZEB binding sites into the promoter region of the ZNF554 locus. Co-transfection with ZEB1/2 led to increased reporter activity in extravillous trophoblasts, which was affected by oxygen concentration. Deletion of CpG in HREs in AluY decreased reporter activity, implying that decreased ZNF554 expression in preterm preeclampsia is epigenetically regulated. The study revealed that evolutionary changes in the ZNF554 locus enabled the regulation of ZNF554 expression by hypoxia and ZEB transcription factors in extravillous trophoblasts, facilitating deep trophoblast invasion in humans. Our data suggest that ZNF554 downregulation by epigenetic mechanisms is involved in preeclampsia pathology." @default.
- W4386640467 created "2023-09-13" @default.
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- W4386640467 date "2023-09-01" @default.
- W4386640467 modified "2023-10-06" @default.
- W4386640467 title "Evolutionary Changes in the Zinc Finger 554 (ZNF554) Locus in Anthropoid Primates: Implications for Deep Placentation and Preeclampsia" @default.
- W4386640467 doi "https://doi.org/10.1016/j.jri.2023.104053" @default.
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