Differential Glucocorticoid Receptor-mediated Transcription Mechanisms
Differential Glucocorticoid Receptor-mediated Transcription Mechanisms
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DOI：
10.1074/jbc.m110.195040
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发表时间：
2011-02-01
影响因子：
4.8
通讯作者：
Archer, Trevor K.
中科院分区：
文献类型：
--
作者：
Aoyagi, Sayura;Archer, Trevor K.
糖皮质激素受体 (GR) 等核受体是配体依赖性转录因子，通过募集调节染色质结构的因子来介导靶基因的转录。在这项研究中，姜黄素（一种已知可抑制 GR 介导的转录的化合物）被用来检查 GR 调节转录的不同机制。通过染色质免疫沉淀和 RT-PCR 实验分析了金属硫因-2A (MT2A) 和溶质载体家族 19 成员 2 (SLC19A2) 这两个 GR 靶基因的转录调控机制，其中激素依赖性基因激活分别受到姜黄素处理的抑制或不影响。数据表明，激素依赖性 MT2A 基因表达的丧失是由于转录机制初始组装后持续转录活性受到抑制所致。相反，激素依赖性 SLC19A2 基因表达得以维持，因为转录机器组装后的持续转录输出不受姜黄素影响。这些结果表明，两个GR靶基因使用替代机制在转录机器组装后持续转录输出的水平上调节表达水平。
Nuclear receptors such as the glucocorticoid receptor (GR) are ligand-dependent transcription factors that mediate transcription of target genes by recruiting factors that modulate chromatin structure. In this study, curcumin, a compound known to inhibit GR-mediated transcription, was used to examine the different mechanisms by which GR regulates transcription. The mechanisms of transcription regulation of metallothioneine-2A (MT2A) and solute carrier family 19 member 2 (SLC19A2), two GR target genes where the hormone-dependent gene activation is inhibited or unaffected by curcumin treatment, respectively, were analyzed by chromatin immunoprecipitation and RT-PCR experiments. The data suggest that the loss of hormone-dependent MT2A gene expression is due to the inhibition of continued transcription activity after initial assembly of the transcription machinery. In contrast, the hormone-dependent SLC19A2 gene expression is maintained because the continued transcription output after assembly of transcription machinery is unaffected by curcumin. These results suggest that the two GR target genes use alternate mechanisms to regulate expression levels at the level of continued transcription output after transcription machinery assembly.