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首页> 外文期刊>Molecular and Cellular Biology >Cell-Specific Interaction of Retinoic Acid Receptors with Target Genes in Mouse Embryonic Fibroblasts and Embryonic Stem Cells
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Cell-Specific Interaction of Retinoic Acid Receptors with Target Genes in Mouse Embryonic Fibroblasts and Embryonic Stem Cells

机译：维甲酸受体与小鼠胚胎成纤维细胞和胚胎干细胞中靶基因的细胞特异性相互作用

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摘要

All-trans retinoic acid (RA) induces transforming growth factor beta (TGF-β)-dependent autocrine growth of mouse embryonic fibroblasts (MEFs). We have used chromatin immunoprecipitation to map 354 RA receptor (RAR) binding loci in MEFs, most of which were similarly occupied by the RARα and RARγ receptors. Only a subset of the genes associated with these loci are regulated by RA, among which are several critical components of the TGF-β pathway. We also show RAR binding to a novel series of target genes involved in cell cycle regulation, transformation, and metastasis, suggesting new pathways by which RA may regulate proliferation and cancer. Few of the RAR binding loci contained consensus direct-repeat (DR)-type elements. The majority comprised either degenerate DRs or no identifiable DRs but anomalously spaced half sites. Furthermore, we identify 462 RAR target loci in embryonic stem (ES) cells and show that their occupancy is cell type specific. Our results also show that differences in the chromatin landscape regulate the accessibility of a subset of more than 700 identified loci to RARs, thus modulating the repertoire of target genes that can be regulated and the biological effects of RA.
机译：全反式维甲酸（RA）诱导小鼠胚胎成纤维细胞（MEF）依赖转化生长因子β（TGF-β）的自分泌生长。我们已使用染色质免疫沉淀法在MEF中定位354个RA受体（RAR）结合位点，其中大多数类似地被RARα和RARγ受体占据。与这些基因座相关的基因只有一个子集受RA调节，其中TGF-β途径的几个关键组成部分。我们还显示了RAR与一系列参与细胞周期调控，转化和转移的新型靶基因的结合，提示RA可能通过其调控增殖和癌症的新途径。很少有RAR结合位点包含共有直接重复（DR）类型的元素。多数包括退化的灾难恢复或没有可识别的灾难恢复，但半个站点的间距异常。此外，我们在胚胎干（ES）细胞中鉴定了462个RAR目标基因座，并表明它们的占据是特定细胞类型的。我们的研究结果还表明，染色质景观的差异调节了700多个已确定基因座的子集对RAR的可及性，从而调节了可调控的靶基因库和RA的生物学效应。

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