Estrogen receptor beta isoforms exhibit differences in ligand-activated transcriptional activity in an estrogen response element sequence-dependent manner.
Estrogen receptor beta isoforms exhibit differences in ligand-activated transcriptional activity in an estrogen response element sequence-dependent manner.
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DOI：
10.1210/en.2003-1043
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发表时间：
2004
期刊：
影响因子：
4.8
通讯作者：
T. Ramsey;K. E. Risinger;S. C. Jernigan;K. Mattingly;C. Klinge
中科院分区：
文献类型：
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作者：
T. Ramsey;K. E. Risinger;S. C. Jernigan;K. Mattingly;C. Klinge
据报道，在瞬时转染细胞中，雌激素受体β（ER β）的雌二醇（E2）诱导的转录活性低于人（h）ER α（来自雌激素反应元件（ERE）驱动的报告基因）。已报告了全长和短hER β [hER β 1，530个氨基酸（aa）;和hER β 1 s，477个aa]活性的验证数据。为了验证hER β 1比hER β 1 s具有更高的转录活性这一假设，我们比较了E2、2，3-二（4-羟基苯基）丙腈（一种选择性ER β激动剂）和白藜芦醇诱导的hER β 1、hER β 1 s和大鼠（r）ER β与hER α在瞬时转染CHO-K1和HEC-1A细胞中不同ERE上的转录。我们的研究结果首次表明，hER β 1具有类似的E2-诱导活性hER α和更大的活性比rER β或hER β 1的共识回文ERE，无论是作为一个单一的或双拷贝;一个最小的ERE;和nonpalindromic pS2 ERE。2，3-双（4-羟基苯基）丙腈对hER β 1和hER β 1的疗效大于对rER β或hER α的疗效。我们发现ER β亚型和ER α之间的转录差异取决于ER序列，证实ER结合的DNA序列是ER作用的变构效应物。对于最小的13 bp ERE和pS2 ERE，hER β 1的转录活性增加与结合亲和力增加相关。辅激活物类固醇受体辅激活物-1和cAMP反应元件结合蛋白结合蛋白协同激活hER α和ER β转录，并显示与rER β和hER β 1的效力降低，这表明ER β 1的N末端在辅激活物相互作用中的作用。总的来说，这些数据表明ER β亚型的细胞表达可能以配体依赖性方式差异性地影响ERE调节的靶基因表达。
Estrogen receptor beta (ERbeta) has been reported to have lower estradiol (E2)-induced transcriptional activity than human (h)ERalpha from estrogen response element (ERE)-driven reporters in transiently transfected cells. Conflicting data for activities of full-length and short hERbeta [hERbeta1, 530 amino acids (aa); and hERbeta1s, 477aa] have been reported. To test the hypothesis that hERbeta1 has higher transcriptional activity than hERbeta1s, we compared E2, 2,3-bis(4-hydroxyphenyl)propionitrile (a selective ERbeta agonist), and resveratrol-induced transcription by hERbeta1, hERbeta1s, and rat (r) ERbeta with hERalpha on different EREs in transiently transfected CHO-K1 and HEC-1A cells. Our results demonstrate for the first time that hERbeta1 has similar E2-induced activity to hERalpha and greater activity than rERbeta or hERbeta1s on a consensus palindromic ERE, either as a single or double copy; a minimal ERE; and the nonpalindromic pS2 ERE. 2,3-Bis(4-hydroxyphenyl)propionitrile showed greater efficacy with hERbeta1 and hERbeta1s than for rERbeta or hERalpha. We found that transcriptional differences between the ERbeta isoforms and ERalpha depend on the ERE sequence, confirming that the DNA sequence bound by ER is an allosteric effector of ER action. For the minimal 13-bp ERE and the pS2 ERE, the increase in transcriptional activity with hERbeta1 correlated with increased binding affinity. Coactivators steroid receptor coactivator-1 and cAMP response element binding protein-binding protein synergistically activated hERalpha and ERbeta transcription and showed reduced efficacy with rERbeta and hERbeta1s, suggesting a role for the N terminus of ERbeta1 in coactivator interaction. Collectively, these data indicate that the cellular expression of ERbeta isoforms may differentially impact ERE-regulated target gene expression in a ligand-dependent manner.