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首页> 外文期刊>Nucleus >Topologically Associating Domains: An invariant framework or a dynamic scaffold?
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Topologically Associating Domains: An invariant framework or a dynamic scaffold?

机译:拓扑关联的域:不变的框架还是动态的支架?

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摘要

Metazoan genomes are organized into regions of topologically associating domains (TADs). TADs are demarcated by border elements, which are enriched for active genes and high occupancy architectural protein binding sites. We recently demonstrated that 3D chromatin architecture is dynamic in response to heat shock, a physiological stress that downregulates transcription and causes a global redistribution of architectural proteins. We utilized a quantitative measure of border strength after heat shock, transcriptional inhibition, and architectural protein knockdown to demonstrate that changes in both transcription and architectural protein occupancy contribute to heat shock-induced TAD dynamics. Notably, architectural proteins appear to play a more important role in altering 3D chromatin architecture. Here, we discuss the implications of our findings on previous studies evaluating the dynamics of TAD structure during cellular differentiation. We propose that the subset of variable TADs observed after differentiation are representative of cell-type specific gene expression and are biologically significant.
机译:后生动物的基因组被组织成拓扑关联域(TAD)的区域。 TAD由边界元素划分,这些元素富含活性基因和高占用率的建筑蛋白结合位点。最近,我们证明了3D染色质结构是动态响应热冲击的,这是一种生理应激,可下调转录并导致建筑蛋白的全局重新分布。我们利用热休克,转录抑制和建筑蛋白敲低后边界强度的定量测量,以证明转录和建筑蛋白占用率的变化都有助于热激诱导的TAD动态。值得注意的是,建筑蛋白似乎在改变3D染色质结构中起着更重要的作用。在这里,我们讨论我们的发现对评估细胞分化过程中TAD结构动力学的先前研究的启示。我们建议分化后观察到的可变TAD的子集代表细胞类型特异性基因表达,并且具有生物学意义。

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