Histone modification levels are predictive for gene expression

Histone modification levels are predictive for gene expression
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DOI:
10.1073/pnas.0909344107
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发表时间:
2010-02-16
影响因子:
11.1
通讯作者:
Vingron, Martin
Vingron, Martin
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Karlic, Rosa;Chung, Ho-Ryun;Vingron, Martin

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组蛋白经常被共价修饰修饰。这些组蛋白修饰被认为参与各种染色质依赖性过程,包括转录。为了阐明组蛋白修饰和转录之间的关系,我们衍生了定量模型来根据组蛋白修饰水平预测基因的表达水平。我们发现组蛋白修饰水平和基因表达密切相关。此外,我们表明只需要少量的组蛋白修饰就可以准确预测基因表达。我们表明,不同组蛋白修饰对于预测由高 CpG 含量启动子 (HCP) 或低 CpG 含量启动子 (LCP) 驱动的基因表达是必要的。涉及 H3K4me3 和 H3K79me1 的定量模型最能预测 LCP 中的表达水平,而 HCP 则需要 H3K27ac 和 H4K20me1。最后,我们表明组蛋白修饰和基因表达之间的联系似乎是普遍的,因为我们能够使用在另一种细胞类型上训练的模型来预测一种细胞类型的基因表达水平。
Histones are frequently decorated with covalent modifications. These histone modifications are thought to be involved in various chromatin-dependent processes including transcription. To elucidate the relationship between histone modifications and transcription, we derived quantitative models to predict the expression level of genes from histone modification levels. We found that histone modification levels and gene expression are very well correlated. Moreover, we show that only a small number of histone modifications are necessary to accurately predict gene expression. We show that different sets of histone modifications are necessary to predict gene expression driven by high CpG content promoters (HCPs) or low CpG content promoters (LCPs). Quantitative models involving H3K4me3 and H3K79me1 are the most predictive of the expression levels in LCPs, whereas HCPs require H3K27ac and H4K20me1. Finally, we show that the connections between histone modifications and gene expression seem to be general, as we were able to predict gene expression levels of one cell type using a model trained on another one.