Androgen receptor epigenetics.
Androgen receptor epigenetics.
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DOI：
10.3978/j.issn.2223-4683.2013.09.02
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发表时间：
2013-09-01
影响因子：
2
通讯作者：
Balk SP
中科院分区：
文献类型：
--
作者：
Cai C;Yuan X;Balk SP
雄激素受体(AR)是一种转录因子，通过调节数百个基因的表达来驱动前列腺上皮的分化。相反，AR在前列腺癌(PCA)的发展中也起着核心作用，它在去势后复发的肿瘤(去势抵抗型前列腺癌，CRPC)中继续活跃。AR的反式激活功能已经得到了广泛的研究，AR还可以作为一组不同基因的转录抑制因子发挥作用，但对前列腺癌至关重要的AR调节基因的识别仍然不清楚。此外，AR在PCa发育和进展过程中获得新功能的程度仍有待确定。最近的研究强调了染色质结构和组蛋白翻译后修饰在确定受AR和所有其他转录因子调控的基因谱中的核心作用。虽然DNA甲基化在基因表达的表观遗传调控中的作用已经得到证实，但现在人们认识到染色质结构在基因表达的表观遗传调控中起着中心和动态的作用。该综述的重点是AR与染色质的相互作用以及它们如何在前列腺癌的发生和发展中调节AR功能。
The androgen receptor (AR) is a transcription factor that drives the differentiation of prostate epithelium by regulating the expression of several hundred genes. Conversely, AR also plays a central role in prostate cancer (PCa) development, and it continues to be active in tumors that relapse after castration (castration-resistant prostate cancer, CRPC). The transactivation function of AR has been extensively studied, and AR can also function as a transcriptional repressor on a distinct set of genes, but the identity of the AR regulated genes that are critical for PCa remain unclear. Moreover, the extent to which AR acquires new functions during PCa development and progression remains to be determined. Recent studies have highlighted the central role of chromatin structure and histone posttranslational modifications in determining the spectrum of genes regulated by AR and all other transcription factors. While the role of DNA methylation in the epigenetic regulation of gene expression is well established, it is now appreciated that chromatin structure plays a central and dynamic role in the epigenetic regulation of gene expression. The focus of this review is on AR interactions with chromatin and how they regulate AR function in PCa development and progression.