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Regulation of target gene expression by the vitamin D receptor - an update on mechanisms

机译:维生素D受体对靶基因表达的调控-机制的最新进展

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Virtually all of the known biological actions of the hormonal ligand 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) are mediated by the vitamin D receptor (VDR). Following binding and activation by the ligand, the VDR localizes in the nucleus to the regulatory regions of target genes and recruits chromatin-active coregulatory complexes which, in turn, modulate transcriptional output. The failure of the VDR to function due to crippling mutations results in total hereditary resistance to 1,25(OH)2D3 in both mice and humans. In this review, we summarize the structural and functional properties of the VDR and the role of 1,25(OH)2D3 in receptor activation, and then describe the results of recent studies using genome-wide analyses that define the overarching principles through which the VDR modulates genes expression. We also focus on the recent analysis of a specific 1,25(OH)2D3 regulated gene that provides confirmation of the principles identified through these genome-wide methodologies. Taken together, these studies suggest an unanticipated increase in the complexity of the molecular processes that govern gene regulation by hormones and other factors.
机译:几乎所有激素配体1,25-二羟基维生素D 3 (1,25(OH) 2 D 3 )的已知生物学作用由维生素D受体(VDR)介导。在被配体结合和激活后,VDR定位在细胞核中靶基因的调节区,并募集染色质活性共调节复合物,进而调节转录输出。 VDR因残废突变而无法发挥功能,导致小鼠和人类对1,25(OH) 2 D 3 的总遗传抵抗力。在这篇综述中,我们总结了VDR的结构和功能特性以及1,25(OH) 2 D 3 在受体激活中的作用,然后描述了结果。最近的研究使用全基因组分析定义了VDR调节基因表达的总体原理。我们还将重点放在对特定的1,25(OH) 2 D 3 调控基因的最新分析中,该基因为通过这些全基因组方法学确定的原理提供了证实。综上所述,这些研究表明,由激素和其他因素控制基因调控的分子过程的复杂性出乎意料地增加了。

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