Functional selectivity of recombinant mammalian SWI/SNF subunits
Functional selectivity of recombinant mammalian SWI/SNF subunits
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DOI：
10.1101/gad.828000
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发表时间：
2000-10-01
影响因子：
10.5
通讯作者：
Emerson, BM
中科院分区：
文献类型：
--
作者：
Kadam, S;McAlpine, GS;Emerson, BM
染色质重塑复合物的SWI/SNF家族在促进特定转录因子与从酵母到人类的多种生物体中的核小体DNA的结合中起着关键作用。然而，SWI/SNF和其他染色质重塑复合物激活特定基因子集的过程知之甚少。我们表明，哺乳动物SWI/SNF调节转录从染色质组装基因在体外的因子特异性的方式。包括EKLF在内的几种锌指蛋白的DNA结合结构域（DBD）直接与SWI/SNE相互作用，在染色质组装的β-珠蛋白启动子内产生DNA酶I超敏性。有趣的是，我们发现两个SWI/SNE亚基（BRG 1和BAF 155）是必要的和足够的靶向染色质重塑和转录激活EKLF在体外。仅用BRG 1-BAF 155最小复合物和EKLE锌指DBD实现重构，而转录另外需要激活结构域。相反，BRG 1-BAF 155复合物不与两种不相关的转录因子TFE 3和NP-κ B相互作用或起作用。我们的结论是，某些转录因子的特定结构域差异靶向SWI/SNF复合物染色质的基因选择性的方式和个人SWI/SNF亚基发挥独特的作用，在转录因子指导的核小体重塑。
The SWI/SNF family of chromatin-remodeling complexes plays a key role in facilitating the binding of specific transcription factors to nucleosomal DNA in diverse organisms from yeast to man. Yet the process by which SWI/SNF and other chromatin-remodeling complexes activate specific subsets of genes is poorly understood. We show that mammalian SWI/SNF regulates transcription from chromatin-assembled genes in a factor-specific manner in vitro. The DNA-binding domains (DBDs) of several zinc finger proteins, including EKLF, interact directly with SWI/SNE to generate DNase I hypersensitivity within the chromatin-assembled beta-globin promoter. Interestingly, we find that two SWI/SNE subunits (BRG1 and BAF155) are necessary and sufficient for targeted chromatin remodeling and transcriptional activation by EKLF in vitro. Remodeling is achieved with only the BRG1-BAF155 minimal complex and the EKLE zinc finger DBD, whereas transcription requires, in addition, an activation domain. In contrast, the BRG1-BAF155 complex does not interact or function with two unrelated transcription factors, TFE3 and NP-kappa B. We conclude that specific domains of certain transcription factors differentially target SWI/SNF complexes to chromatin in a gene-selective manner and that individual SWI/SNF subunits play unique roles in transcription factor-directed nucleosome remodeling.