Estrogen-related receptor ERRα-mediated downregulation of human hydroxysteroid sulfotransferase (SULT2A1) in Hep G2 cells.
Estrogen-related receptor ERRα-mediated downregulation of human hydroxysteroid sulfotransferase (SULT2A1) in Hep G2 cells.
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DOI：
10.1016/j.cbi.2011.04.002
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发表时间：
2011-07-15
影响因子：
5.1
通讯作者：
Chen, Guangping
中科院分区：
文献类型：
--
作者：
Huang, Chaoqun;Zhou, Tianyan;Chen, Yue;Sun, Teng;Zhang, Shufen;Chen, Guangping
羟基类固醇磺基转移酶SULT 2A 1催化羟基类固醇和异生物质的硫酸化。它在含羟基异生物质的解毒和羟基甾体生物活性的调节中起重要作用。ERRα是核受体超家族的孤儿成员，与雌激素受体α（ERα）密切相关。我们报道ERRα抑制Hep G2细胞中SULT 2A 1 mRNA的表达。为了研究这种调控机制，我们研究了ERRα对Hep G2细胞中人SULT 2A 1启动子转录的影响。报告基因荧光素酶检测结果显示ERRα可显著抑制人SULT 2A 1启动子在Hep G2细胞中的转录。缺失分析表明，人类SULT 2A 1启动子区域的-188和-130位置之间是必要的，它的阻遏ERRα在Hep G2细胞。人SULT 2A 1的5' DNA −188至−130区域包含IR 2和DR 4激素反应元件和两个推定的ERRα反应元件（ERRE）（ERRE 188：GCAAGCTCA和ERRE 155：ATAAGTTCA）。有趣的是，ERRE 188与IR 2元件重叠，ERRE 155与DR 4元件重叠。我们的进一步研究表明ERRα通过与其他核受体竞争结合IR 2或DR 4元件来抑制人SULT 2A 1启动子的转录。电泳迁移率变动分析（EMSA）和染色质免疫沉淀（ChIP）分析证实了ERRE 188和ERRE 155元件与ERRα的相互作用。我们的研究结果表明ERRα可能在调节药物和外源性物质的代谢以及通过SULT 2A 1调节内源性羟基类固醇活性方面发挥重要作用。
Hydroxysteroid sulfotransferase SULT2A1 catalyzes the sulfation of hydroxysteroids and xenobiotics. It plays an important role in the detoxification of hydroxyl-containing xenobiotics and in the regulation of the biological activities of hydroxysteroids. ERRα is an orphan member of the nuclear receptor superfamily that is closely related to estrogen receptor alpha (ERα). Here we report that the mRNA expression of human SULT2A1 was suppressed by ERRα in Hep G2 cells. To investigate the mechanisms of this regulation, the effects of ERRα on human SULT2A1 promoter transcription in Hep G2 cells were investigated. Reporter luciferase assay results showed that ERRα significantly represses human SULT2A1 promoter transcription in Hep G2 cells. Deletion analysis indicated that human SULT2A1 promoter region between positions −188 and −130 is necessary for its repression by ERRα in Hep G2 cells. The 5’ DNA −188 to −130 region of human SULT2A1 contains IR2 and DR4 hormone response elements and two putative ERRα response elements (ERREs) (ERRE188: GCAAGCTCA and ERRE155: ATAAGTTCA). Interestingly, ERRE188 overlaps with the IR2 element and ERRE155 overlaps with the DR4 element. Our further investigation demonstrated that ERRα represses human SULT2A1 promoter transcription by competing with other nuclear receptors for binding to IR2 or DR4 elements. The interaction of ERRE188 and ERRE155 elements with ERRα was confirmed by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) analysis. Our results suggest that ERRα may play an important role in regulating the metabolism of drugs and xenobiotics and in regulating endogenous hydroxysteroid activities via the regulation of SULT2A1.
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影响因子：
4.8
作者：
Seely, J;Amigh, KS;Rainey, WE
通讯作者：
Rainey, WE
影响因子：
3.5
作者：
Seo, Young-Kyo;Chung, Yoon-Tae;Chatterjee, Bandana
通讯作者：
Chatterjee, Bandana
影响因子：
--
作者：
HOLT, PR
通讯作者：
HOLT, PR
影响因子：
64.8
作者：
GIGUERE, V;YANG, N;EVANS, RM
通讯作者：
EVANS, RM
孤儿雌激素受体相关受体α（Erralpha）在整个成骨细胞分化中表达，并在体外调节骨形成。
影响因子：
7.8
作者：
Bonnelye, E;Merdad, L;Kung, V;Aubin, J E
通讯作者：
Aubin, J E