Transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases
Transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases
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DOI：
10.1074/jbc.m312300200
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发表时间：
2004-06-04
影响因子：
4.8
通讯作者：
Seiser, C
中科院分区：
文献类型：
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作者：
Kurtev, V;Margueron, R;Seiser, C
组蛋白乙酰转移酶和脱乙酰基酶被转录因子和接头蛋白招募来调节特定的靶基因亚群。我们感兴趣的是确定组蛋白脱乙酰基酶1(HDAC1)的相互作用伙伴，这些伙伴可能参与授予靶标或底物的特异性。利用酵母双杂交系统，我们分离了雌激素受体活性抑制因子(REA)，这是一种新的HDAC1相关蛋白。我们证明了REA与HDAC1在体内的相互作用，并表征了它们在体外相互作用所需的各自结构域。此外，我们还发现REA还与第二类组蛋白去乙酰基酶HDAC5有关。在荧光素酶报告基因分析中，REA抑制转录，并且这种抑制对去乙酰化酶抑制剂曲古菌素A敏感。最后，我们发现REA与鸡卵蛋白上游结合转录因子和II特异地相互作用。核受体鸡卵蛋白上游结合转录因子I被发现与REA和组蛋白脱乙酰基酶协同抑制靶基因。因此，我们提出了REA的一种新的功能，即通过组蛋白脱乙酰基酶的募集，作为核激素受体转录抑制的中介。
Histone acetyltransferases and deacetylases are recruited by transcription factors and adapter proteins to regulate specific subsets of target genes. We were interested in identifying interaction partners of histone deacetylase 1 (HDAC1) that might be involved in conferring target or substrate specificity. Using the yeast two-hybrid system, we isolated the repressor of estrogen receptor activity ( REA) as a novel HDAC1-associated protein. We demonstrated the in vivo interaction of REA with HDAC1 and characterized the respective domains required for their interaction in vitro. In addition, we found that REA also associates with the class II histone deacetylase HDAC5. In luciferase reporter assays, REA decreased transcription, and this repression was sensitive to the deacetylase inhibitor trichostatin A. Finally, we showed that REA specifically interacts with the chicken ovalbumin upstream binding transcription factors and II. The nuclear receptor chicken ovalbumin upstream binding transcription factor I was found to cooperate with REA and histone deacetylases in the repression of target genes. We, therefore, propose a novel function for REA as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases.