HoxA-11 and FOXO1A Cooperate to Regulate Decidual Prolactin Expression: Towards Inferring the Core Transcriptional Regulators of Decidual Genes

作者: Vincent J. Lynch , Kathryn Brayer , Birgit Gellersen , Günter P. Wagner

DOI: 10.1371/JOURNAL.PONE.0006845

关键词: Transcription factorEndocrinologyCell biologyEnhancerDecidualizationBiologyGene expressionRegulation of gene expressionCellular differentiationInternal medicineChromatin immunoprecipitationActivator (genetics)

摘要: Background During the menstrual cycle, ovarian steroid hormones estrogen and progesterone control a dramatic transcriptional reprogramming of endometrial stromal cells (ESCs) leading to receptive state for blastocyst implantation establishment pregnancy. A key marker gene this decidualization process is prolactin gene. Several regulators have been identified that are essential ESCs, including Hox genes HoxA-10 HoxA-11, forkhead box FOXO1A. While previous studies downstream target FOXO1A, role HoxA-11 in has not investigated. Here, we show required expression decidualized ESC. alone repressor on decidual promoter, it turns into an activator when combined with Conversely, HoxA-10, which previously shown associate FOXO1A upregulate IGFBP-1 expression, unable PRL co-expressed By co-immunoprecipitation chromatin immunoprecipitation, demonstrate physical association binding both factors enhancer region (−395 −148 relative start site) promoter. Because induced upon decidualization, serves assemble decidual-specific complex HoxA-11. These data highlight cooperativity between numerous transcription differentiating ESC, suggest core set physically functionally interact drive battery upregulated differentiated In addition, functional non-equivalence respect regulation suggests these regulate distinct sets during decidualization.

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