Target specificities of estrogen receptor-related receptors:: Analysis of binding sequences and identification of Rb1-inducible coiled-coil 1 (Rb1cc1) as a target gene
Target specificities of estrogen receptor-related receptors:: Analysis of binding sequences and identification of Rb1-inducible coiled-coil 1 (Rb1cc1) as a target gene
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DOI：
10.1093/jb/mvm231
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发表时间：
2008-03-01
影响因子：
2.7
通讯作者：
Osumi, Takashi
中科院分区：
文献类型：
--
作者：
Akter, Mst. Hasina;Chano, Tokuhiro;Osumi, Takashi
雌激素受体相关受体（ERRs）是核受体超家族的孤儿成员。一个单一的AGGTCA序列元件前面的三个保守的核苷酸已被确定为一个特定的识别基序的ERRs。在这里，我们对所有三种ERR亚型（α、β和γ）的靶序列进行了系统分析。在电泳凝胶迁移率变动分析和转录报告基因分析中，它们表现出相似的识别特异性模式，显示出极宽的靶序列范围。我们在小鼠启动子数据库中搜索携带可能的ERR结合序列的基因。Rb-1可诱导卷曲螺旋1（Rb 1cc 1）基因启动子区含有两个ERR结合元件，分别命名为反应元件（RE）-1和RE-2。在基因报告基因分析中，RE-2，而不是RE-1，作为一个有效的顺式调节元件的反式激活ERR α的存在下，过氧化物酶体增殖物激活受体γ共激活因子-1 α。突变分析表明，RE-2被ERR α部分识别为单价元件，但也作为由四个间隔核苷酸分隔的直接重复基序。在体内结合ERRa的Rb 1cc 1启动子区的染色质免疫沉淀试验证实。因此，Rb 1cc 1是ERR（x）的靶基因，由一种新型识别序列驱动。
Estrogen receptor-related receptors (ERRs) are orphan members of the nuclear receptor superfamily. A single AGGTCA sequence element preceded by three conserved nucleotides has been identified as a specific recognition motif of ERRs. Here we performed systematic analyses of target sequences on all three ERR subtypes, alpha, beta and gamma. In electrophoretic gel-mobility shift assay and transcriptional reporter assays, they exhibited similar patterns of recognition specificities, showing extremely broad ranges of target sequences. We searched a mouse promoter database for a gene carrying possible ERR-binding sequences. The Rb-1 inducible coiled-coil 1 (Rb1cc1) gene was found to contain two putative ERR binding elements, named response element (RE)-1 and RE-2, in the promoter region. In gene reporter assays, RE-2, but not RE-1, functioned as an effective cis-regulatory element for transactivation by ERR alpha in the presence of a coactivator, peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Mutational analyses suggested that RE-2 is recognized by ERR alpha partly as a monovalent element, but also as a direct repeat motif separated by four spacer nucleotides. In vivo binding of ERRa to the Rb1cc1 promoter region was confirmed by the chromatin immunoprecipitation assay. Thus, Rb1cc1 is a target gene of ERR(x, driven by a novel type of recognition sequence.