Max-Planck-Institut für Molekulare Genetik, Department of Computational Molecular Biology, Ihnestrasse 73, 14195 Berlin, Germany.
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2926-31. doi: 10.1073/pnas.0909344107. Epub 2010 Feb 1.
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.
组蛋白经常被加上共价修饰。这些组蛋白修饰被认为参与各种依赖染色质的过程，包括转录。为了阐明组蛋白修饰与转录之间的关系，我们构建了定量模型，从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与基因表达高度相关。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。我们还表明，需要不同的组蛋白修饰集来预测由高 CpG 含量启动子 (HCPs) 或低 CpG 含量启动子 (LCPs) 驱动的基因表达。涉及 H3K4me3 和 H3K79me1 的定量模型是预测 LCPs 中表达水平最具预测性的模型，而 HCPs 需要 H3K27ac 和 H4K20me1。最后，我们表明，组蛋白修饰与基因表达之间的联系似乎是普遍的，因为我们可以使用基于另一种细胞类型训练的模型来预测一种细胞类型的基因表达水平。
