HMG I/Y regulates long-range enhancer-dependent transcription on DNA and chromatin by changes in DNA topology
HMG I/Y regulates long-range enhancer-dependent transcription on DNA and chromatin by changes in DNA topology
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DOI：
10.1093/nar/28.13.2541
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发表时间：
2000-07-01
影响因子：
14.9
通讯作者：
Emerson, BM
中科院分区：
文献类型：
--
作者：
Bagga, R;Michalowski, S;Emerson, BM
通过远端增强子进行转录调节所需的核结构的性质尚不清楚。我们证明，通过将 DNA 结构蛋白 HMG I/Y 添加到亲和力富集的孔 RNA 聚合酶 II 复合物中，可以在体外实现长程增强子依赖性 β-珠蛋白转录。在该系统中，HMG I/Y 在缺乏相关增强子的情况下抑制启动子活性，并在存在远端增强子的情况下强烈激活转录。重要的是，核小体形成对于体外远程增强子调节既不是必需的，也不在不添加 HMG I/Y 的情况下充分形成，因此，HMG I/Y 对 DNA 结构的调节是 DNA 和染色质组装基因上远程增强子功能的关键调节器。电子显微镜分析表明，HMG I/Y 协同结合到首选 DNA 位点以产生不同的 在存在或不存在 β-珠蛋白增强子的情况下形成环状结构，使远端增强子能够强烈调节基因表达的 DNA 拓扑的形成是 HMG I/Y 和裸露 DNA 的固有特性。
The nature of nuclear structures that are required to confer transcriptional regulation by distal enhancers is unknown. We show that long-range enhancer-dependent beta-globin transcription is achieved in vitro upon addition of the DNA architectural protein HMG I/Y to affinity-enriched hole RNA polymerase II complexes. In this system, HMG I/Y represses promoter activity in the absence of an associated enhancer and strongly activates transcription in the presence of a distal enhancer. Importantly, nucleosome formation is neither necessary for long-range enhancer regulation in vitro nor sufficient without the addition of HMG I/Y, Thus, the modulation of DNA structure by HMG I/Y is a critical regulator of long-range enhancer function on both DNA and chromatin-assembled genes, Electron microscopic analysis reveals that HMG I/Y binds cooperatively to preferred DNA sites to generate distinct looped structures in the presence or absence of the beta-globin enhancer, The formation of DNA topologies that enable distal enhancers to strongly regulate gene expression is an Intrinsic property of HMG I/Y and naked DNA.