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• W2752675944 abstract "To define the transcriptome regulated by Promyelocytic Leukemia Zinc Finger (PLZF) and required for decidualization of human endometrial stromal cells (hESCs). Bioinformatic and integrative analysis of transcriptome changes that occur with downregulation of PLZF expression during decidualization of primary hESCs in culture. Primary hESCs isolated from 3 volunteers were cultured and in vitro decidualized. Knockdown of gene expression was achieved through siRNA transfection. Gene expression changes during decidualization were evaluated by quantitative PCR analysis and western. Genome-wide transcription factor binding was identified using chromatin immunoprecipitation followed by next generation sequencing (ChIP-Seq) whereas global transcriptional changes were annotated using RNA-Seq followed with bioinformatics analysis with paired statistics. PLZF expression is rapidly induced by progesterone in human and murine ESCs. Using ChIP-Seq and ChIP-qPCR, we demonstrate that the progesterone receptor directly binds to the human PLZF gene. Importantly, PLZF knockdown inhibits hESC decidualization in vitro. Integration of ChIP-Seq and RNA-Seq datasets reveals that PLZF governs defined functional subsets of target genes in hESCs including genes involved in cell division, immunomodulation, and cytokine signaling. PLZF directly binds and controls the expression of early growth response (EGR) transcription factor family members: EGR-1 and -2. Importantly, perturbation of levels of EGRs compromises progesterone-dependent decidualization. Therefore, our investigations establish the PLZF transcription factor as a pivotal direct mediator of progesterone-dependent hESC decidualization. PLZF controls the expression of not only a subset of known early signals of decidualization but also previously unsuspected genes responsible for cell division, differentiation, survival, and motility—cellular processes required for the development or function of the decidual cell in vivo. Our current and future studies will use a novel conditional PLZF knockout mouse to confirm the importance of PLZF in endometrial decidualization in vivo. The identification of PLZF and its molecular targets in decidualizing hESCs not only significantly expands our mechanistic insight into endometrial decidualization but may provide new molecular hallmarks of endometrial pathology that can be used for the clinical diagnosis, prognosis, and management of female sub-fecundity and infertility based on a dysfunctional endometrium." @default.
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• W2752675944 date "2017-09-01" @default.
• W2752675944 modified "2023-09-30" @default.
• W2752675944 title "The promyelocytic leukemia Zinc finger transcription factor is required for human endometrial stromal cell decidualization" @default.
• W2752675944 doi "https://doi.org/10.1016/j.fertnstert.2017.07.1051" @default.
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