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Intrinsic disorder in transcription factors

机译:转录因子中的内在疾病

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Intrinsic disorder (ID) is highly abundant in eukaryotes, which reflect the greater need for disorder-associated signaling and transcriptional regulation in nucleated cells. Although several well-characterized examples of intrinsically disordered proteins in transcriptional regulation have been reported, no systematic analysis has been reported so far. To test for the general prevalence of intrinsic disorder in transcriptional regulation, we used the predictor of natural disorder regions (PONDR) to analyze the abundance of intrinsic disorder in three transcription factor datasets and two control sets. This analysis revealed that from 94.13 to 82.63% of transcription factors possess extended regions of intrinsic disorder, relative to 54.51 and 18.64% of the proteins in two control datasets, which indicates the significant prevalence of intrinsic disorder in transcription factors. This propensity of transcription factors to intrinsic disorder was confirmed by cumulative distribution function analysis and charge-hydropathy plots. The amino acid composition analysis showed that all three transcription factor datasets were substantially depleted in order-promoting residues and significantly enriched in disorder-promoting residues. Our analysis of the distribution of disorder within the transcription factor datasets revealed that (a) the AT-hooks and basic regions of transcription factor DNA-binding domains are highly disordered; (b) the degree of disorder in transcription factor activation regions is much higher than that in DNA-binding domains; (c) the degree of disorder is significantly higher in eukaryotic transcription factors than in prokaryotic transcription factors; and (d) the level of alpha-MoRF (molecular recognition feature) prediction is much higher in transcription factors. Overall, our data reflected the fact that eukaryotes with well-developed gene transcription machinery require transcription factor flexibility to be more efficient.
机译:固有疾病(ID)在真核生物中高度丰富,这反映了对核细胞中的无序相关信号传导和转录调节的更高需求。据报道,若干特征在于在转录调节中的本质无序蛋白质的实例,但到目前为止没有报告系统分析。为了测试转录调节中内在病症的一般性患病率,我们使用了自然紊乱区(POLTR)的预测因子来分析三个转录因子数据集和两个控制集中的内在病症的丰度。该分析表明,94.13至82.63%的转录因子具有相对于两个对照数据集中的54.51和18.64%的蛋白质的内在病症的扩展区域,这表明转录因子中的内在病症的显着普及。通过累积分布函数分析和充电 - 水肿切片证实了这种转录因子对内在病症的倾向。氨基酸组成分析表明,所有三种转录因子数据集基本上在促进残留物中基本上耗尽,并且在促进疾病促进残留物中显着富集。我们对转录因子数据集内的病症分布的分析显示(a)转录因子DNA结合结构域的钩和基本区域是高度无序的; (b)转录因子激活区的病症程度远高于DNA结合结构域中的疾病程度; (c)真核转录因子的疾病程度明显高于原核转录因子; (d)转录因子中α-Morf(分子识别特征)预测的水平高得多。总的来说,我们的数据反映了具有良好的基因转录机械的真核生物需要转录因子的灵活性更有效。

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