Modulation of thyroid hormone receptor transactivation by the early region 1A (E1A)-like inhibitor of differentiation 1 (EID1)
Modulation of thyroid hormone receptor transactivation by the early region 1A (E1A)-like inhibitor of differentiation 1 (EID1)
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早期区域 1A (E1A) 样分化抑制剂 1 (EID1) 对甲状腺激素受体反式激活的调节
DOI：
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
F. Lizcano
中科院分区：
文献类型：
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作者：
Diana Vargas;L. Celis;C. Romero;F. Lizcano
甲状腺激素对靶基因的影响介导的转录激活（TA）需要共激活蛋白，如早期1A区（E1A）相关的300 kDa结合蛋白（p300）和cAMP反应元件结合蛋白（CREB）结合蛋白（CBP），即p300/CBP复合物，它们使组蛋白3和4乙酰化，从而允许转录机制进入靶基因启动子。关于p300在甲状腺激素受体（TR）介导的TA中的作用知之甚少，但E1A样分化抑制剂1 （EID1）是p300组蛋白乙酰转移酶（HAT）的抑制剂，是E1A的功能同源物，可能抑制肌源性分化因子D （MyoD）的转录活性并减少肌肉细胞分化。我们通过转染和哺乳动物双杂交研究评估了EID1对TR介导的转录活性的影响，结果表明EID1可能部分降低了TR受体的TA活性，这可能是由于p300的阻断，因为EID1突变体不能降低TR介导的TA。EID1不影响p160共激活蛋白（类固醇受体共激活蛋白的160 kDa蛋白）的功能，并且在功能上独立于共抑制蛋白或TR结合。综上所述，EID1通过阻断p300降低tr介导的转录活性，并可能在肌肉和其他组织中甲状腺受体活性中发挥重要作用。
Transcriptional activation (TA) mediated by the effect of thyroid hormones on target genes requires co-activator proteins such as the early region 1A (E1A) associated 300 kDa binding protein (p300) and the cAMP response element binding protein (CREB) binding protein (CBP), known as the p300/CBP complex, which acetylate histones 3 and 4 to allow transcriptional machinery access to the target gene promoter. Little is known on the role of p300 in thyroid hormone receptor (TR) mediated TA but the E1A-like inhibitor of differentiation 1 (EID1), an inhibitor of p300 histone acetyltransferase (HAT), is a functional homolog of E1A and may inhibit myogenic differentiation factor D (MyoD) transcriptional activity and reduces muscle cell differentiation. We evaluated the influence of EID1 on TR-mediated transcriptional activity using transfection and mammalian two-hybrid studies to show that EID1 may partially reduces TA activity of the TR receptor, probably due to p300 blockage since EID1 mutants cannot reduce TR-mediated TA. The EID1 does not affect the function of p160 co-activator proteins (160 kDa proteins of steroid receptor co-activators) and is functionally independent of co-repressor proteins or TR binding. Summarizing, EID1 reduces TR-mediated transcriptional activity by blocking p300 and may play an important role in thyroid receptor activity in muscle and other tissues.
DOI：
10.1073/pnas.0501491102
发表时间：
2005-05-03
影响因子：
11.1
作者：
Meng, XW;Webb, P;Walfish, PG
通讯作者：
Walfish, PG