Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, United States.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, United States.
J Steroid Biochem Mol Biol. 2014 Oct;144 Pt A:5-11. doi: 10.1016/j.jsbmb.2013.11.004. Epub 2013 Nov 12.
Initial research focused upon several known genetic targets provided early insight into the mechanism of action of the vitamin D hormone (1,25-dihydroxyvitamin D3 (1,25(OH)2D3)). Recently, however, a series of technical advances involving the coupling of chromatin immunoprecipitation (ChIP) to unbiased methodologies that initially involved tiled DNA microarrays (ChIP-chip analysis) and now Next Generation DNA Sequencing techniques (ChIP-seq analysis) has opened new avenues of research into the mechanisms through which 1,25(OH)2D3 regulates gene expression. In this review, we summarize briefly the results of this early work and then focus on more recent studies in which ChIP-chip and ChIP-seq analyses have been used to explore the mechanisms of 1,25(OH)2D3 action on a genome-wide scale providing specific target genes as examples. The results of this work have advanced our understanding of the mechanisms involved at both genetic and epigenetic levels and have revealed a series of new principles through which the vitamin D hormone functions to control the expression of genes. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.
最初的研究集中在几个已知的遗传靶标上,这些靶标为维生素 D 激素(1,25-二羟维生素 D3(1,25(OH)2D3))的作用机制提供了早期的见解。然而,最近一系列涉及染色质免疫沉淀(ChIP)与最初涉及平铺 DNA 微阵列(ChIP-chip 分析)和现在的下一代 DNA 测序技术(ChIP-seq 分析)的无偏方法相结合的技术进步,为研究 1,25(OH)2D3 调节基因表达的机制开辟了新的途径。在这篇综述中,我们简要总结了早期工作的结果,然后重点介绍了最近的研究,这些研究使用 ChIP-chip 和 ChIP-seq 分析来探索 1,25(OH)2D3 在全基因组范围内作用的机制,并以特定的靶基因为例。这项工作的结果提高了我们对遗传和表观遗传水平所涉及的机制的理解,并揭示了一系列维生素 D 激素通过这些机制发挥作用来控制基因表达的新原则。本文是题为“第 16 届维生素 D 研讨会”的特刊的一部分。