Response element sequence modulates estrogen receptor α and β affinity and activity

Response element sequence modulates estrogen receptor α and β affinity and activity
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DOI:
10.1677/jme.0.0290137
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发表时间:
2002-08-01
影响因子:
3.5
通讯作者:
Klinge, CM
Klinge, CM
中科院分区:
医学3区
文献类型:
--
作者:
Kulakosky, PC;McCarty, MA;Klinge, CM

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雌激素受体(ER)-雌激素反应元件(ERE)结合亲和力和雌二醇(E-2)诱导的转录之间的关系尚未得到系统或定量的测试。我们研究了ERE回文长度和3' ERE侧翼序列对ER α和ER β体外亲和力结合的影响以及对转染细胞中报告基因活性的诱导的影响。在13 bp的ERE回文序列的每个臂中添加一个核苷酸,形成15 bp的ERE回文序列,增加了ER α和ERP的亲和力和转录。相比之下,增加一个AT丰富的侧翼序列的基因高度刺激的E,亲和力或报告基因的活性几乎没有影响。ER α和ER β之间的显著差异包括:ER α的K-d和转录诱导通常高于ER β,ER α的ERE回文长度与转录诱导之间的相关性优于ER β,ER α的(ER-ERE)K与转录诱导之间的相关性优于ER β。
The relationship between estrogen receptor (ER)-estrogen response element (ERE) binding affinity and estradiol (E-2)-induced transcription has not been systematically or quantitatively tested. We examined the influence of ERE palindrome length and the 3' ERE flanking sequence on ERalpha and ERbeta affinity binding in vitro and on the induction of reporter gene activity in transfected cells. The addition of one nucleotide in each arm of the 13 bp ERE palindrome, forming a 15 bp ERE palindrome, increased ERalpha and ERP affinity and transcription. In contrast, the addition of an AT-rich flanking sequence from genes highly stimulated by E, had little effect on affinity or reporter gene activity. Notable differences between ERalpha and ERbeta include: both K-d and transcriptional induction were generally higher for ERalpha than ERbeta, better correlation between ERE palindrome length and transcriptional induction for ERalpha than ERbeta, and a better correlation between (ER-ERE) K, and transcriptional induction for ERalpha than for ERbeta.