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首页> 外文期刊>AIMS Genetics >Nucleosome dynamics: HMGB1 facilitates nucleosome restructuring and collaborates in estrogen-responsive gene expression
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Nucleosome dynamics: HMGB1 facilitates nucleosome restructuring and collaborates in estrogen-responsive gene expression

机译：核小体动力学：HMGB1促进核小体重组并在雌激素反应性基因表达中协同作用

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The genome in the human cell is extraordinarily compacted in the nucleus. As a result, much of the DNA is inaccessible and functionally inert. Notwithstanding the highly efficient packaging, mechanisms have evolved to render DNA sites accessible that then enable a multitude of factors to carry out ongoing and vital functions. The compaction is derived from DNA complexation within nucleosomes, which can further consolidate into a higher-order chromatin structure. The nucleosome and nucleosomal DNA are not static in nature, but are dynamic, undergoing structural and functional changes as the cell responds to stresses and/or metabolic or environmental cues. We are only beginning to understand the forces and the complexes that engage the nucleosome to unearth the tightly bound and inaccessible DNA sequences and provide an opening to more accessible target sites. In many cases, current findings support a major role for the action of ATP-dependent chromatin remodeling complexes (CRCs) in providing an avenue to factor accessibility that leads to the activation of transcription. The estrogen receptor α (ERα) does not bind to the estrogen response element (ERE) in the canonical nucleosome. However, evidence will be presented that HMGB1 restructures the nucleosome in an ATP-independent manner and also facilitates access and strong binding of ERα to ERE. The features that appear important in the mechanism of action for HMGB1 will be highlighted, in addition to the characteristic features of the restructured nucleosome. These findings, together with previous evidence, suggest a collaborative role for HMGB1 in the step-wise transcription of estrogen-responsive genes. In addition, alternate mechanistic pathways will be discussed, with consideration that “HMGB1 restructuring” of the nucleosome may generally be viewed as a perturbation of the equilibrium of an ensemble of nearly isoenergetic nucleosome states in an energy landscape that is driven by conformational selection by HMGB1.
机译：人类细胞中的基因组非常紧密地聚集在细胞核中。结果，许多DNA难以接近且在功能上是惰性的。尽管包装效率很高，但已经开发出使DNA位点可访问的机制，然后使多种因素能够执行正在进行的重要功能。紧缩来自核小体中的DNA络合，它可以进一步整合为更高阶的染色质结构。核小体和核小体DNA本质上不是静态的，而是动态的，随着细胞对压力和/或代谢或环境提示的反应而发生结构和功能变化。我们才刚刚开始了解与核小体结合以释放紧密结合且难以接近的DNA序列的力和复合物，并为更易接近的靶位点提供了开口。在许多情况下，当前的发现支持ATP依赖的染色质重塑复合物（CRC）作用的主要作用，为因子可及性提供途径，从而导致转录激活。雌激素受体α（ERα）不与规范核小体中的雌激素反应元件（ERE）结合。但是，将提供证据表明HMGB1以不依赖ATP的方式重组核小体，也有助于ERα的进入和与ERE的牢固结合。除了重组核小体的特征外，还将突出显示对于HMGB1的作用机制很重要的特征。这些发现以及以前的证据表明，HMGB1在雌激素反应性基因的逐步转录中具有协同作用。此外，将讨论替代的机理途径，考虑到核小体的“ HMGB1重组”通常可被视为是由HMGB1构象选择驱动的能量格局中几乎同能的核小体态集合的平衡的扰动。 。

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