The Global Relationship between Chromatin Physical Topology, Fractal Structure, and Gene Expression.
The Global Relationship between Chromatin Physical Topology, Fractal Structure, and Gene Expression.
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染色质物理拓扑，分形结构和基因表达之间的全球关系。
DOI：
10.1038/srep41061
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发表时间：
2017-01-24
影响因子：
4.6
通讯作者：
Backman V
中科院分区：
文献类型：
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作者：
Almassalha LM;Tiwari A;Ruhoff PT;Stypula-Cyrus Y;Cherkezyan L;Matsuda H;Dela Cruz MA;Chandler JE;White C;Maneval C;Subramanian H;Szleifer I;Roy HK;Backman V
我们对基因转录的大多数了解来自于细胞作为分子机器的观点：关注分子修饰对蛋白质的作用，这些蛋白质在逐个基因座的基础上进行转录反应。这种观点忽略了一个关键的现实：生物反应不是发生在一个空的空间，而是发生在一个高度复杂，相互关联和密集的纳米环境中，深刻影响化学相互作用。我们探索了染色质的物理纳米环境与基因转录之间的关系。我们分析表明，在染色质的分形维数，D，对应于同时增加染色质的可及性和压实异质性的变化。使用这些预测，我们实验证明，在30分钟内染色质D的纳米级变化与伴随的转录增强和抑制相关。此外，我们发现，由于分形维数的增加，染色质的物理结构的异质性增加与基因网络的异质性增加相关。这些发现表明，染色质拓扑结构的高阶折叠可能作为一个分子通路独立的代码调节基因表达的全球模式。由于染色质的物理组织在肿瘤发生中经常改变，这项工作为肿瘤发生过程中经常改变的过程提供了分子功能与物理结构配对的证据。
Most of what we know about gene transcription comes from the view of cells as molecular machines: focusing on the role of molecular modifications to the proteins carrying out transcriptional reactions at a loci-by-loci basis. This view ignores a critical reality: biological reactions do not happen in an empty space, but in a highly complex, interrelated, and dense nanoenvironment that profoundly influences chemical interactions. We explored the relationship between the physical nanoenvironment of chromatin and gene transcription in vitro. We analytically show that changes in the fractal dimension, D, of chromatin correspond to simultaneous increases in chromatin accessibility and compaction heterogeneity. Using these predictions, we demonstrate experimentally that nanoscopic changes to chromatin D within thirty minutes correlate with concomitant enhancement and suppression of transcription. Further, we show that the increased heterogeneity of physical structure of chromatin due to increase in fractal dimension correlates with increased heterogeneity of gene networks. These findings indicate that the higher order folding of chromatin topology may act as a molecular-pathway independent code regulating global patterns of gene expression. Since physical organization of chromatin is frequently altered in oncogenesis, this work provides evidence pairing molecular function to physical structure for processes frequently altered during tumorigenesis.