Histone modifications play critical roles in mammalian development, regulating chromatin structure and gene expression. Dynamic histone modifications among cell types have been shown to associate with changes in mammalian development. However, how to quantitatively measure the histone modification alterations and how histone modifications vary across cell types under different genetic contexts remain largely unexplored and whether these changes are related to the primary DNA sequence remains limited. Here, we employed an entropy-based method to measure histone modification alterations in six definite genomic regions across five cell types and identified lineage-specific histone modification genes. We observed that histone modification alterations prefer to enrich in 5'-UTR exons, and also in 3'-UTR exons and its downstream. Then we built a model to predict the histone modification patterns from the primary DNA sequence. We found that the frequencies of k-mer sequence compositions are predictive of histone modification patterns, suggesting that the primary DNA sequence correlated with the histone modification alterations among cell types. Additionally, the lineage-specific histone modification genes display a higher conservation and lower GC-content. Together, we performed a systematic analysis for histone modification alterations and demonstrated how to identify genomic region-specific elements of epigenetic and genetic regulation and histone modification patterns across different cell types.

中文翻译：

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遗传背景表征细胞类型之间的动态组蛋白修饰模式。

组蛋白修饰在哺乳动物发育，调节染色质结构和基因表达中起关键作用。已经显示细胞类型之间的动态组蛋白修饰与哺乳动物发育的变化有关。然而，如何定量测量组蛋白修饰的变化以及组蛋白修饰如何在不同遗传背景下跨细胞类型变化的方法仍大有待探索，而且这些变化是否与一级DNA序列有关仍很有限。在这里，我们采用了一种基于熵的方法来测量横跨五种细胞类型的六个确定基因组区域中的组蛋白修饰变化，并确定了谱系特异性的组蛋白修饰基因。我们观察到，组蛋白修饰的改变倾向于富含5'-UTR外显子，以及3'-UTR外显子及其下游。然后，我们建立了一个模型，可以根据一级DNA序列预测组蛋白修饰模式。我们发现k-mer序列组成的频率是组蛋白修饰模式的预测，表明一级DNA序列与细胞类型之间的组蛋白修饰变化相关。另外，谱系特异性的组蛋白修饰基因显示出更高的保守性和更低的GC含量。在一起，我们对组蛋白修饰的变化进行了系统分析，并展示了如何识别表观遗传和遗传调控的基因组区域特异性元件以及跨不同细胞类型的组蛋白修饰模式。我们发现k-mer序列组成的频率是组蛋白修饰模式的预测，表明一级DNA序列与细胞类型之间的组蛋白修饰变化相关。另外，谱系特异性的组蛋白修饰基因显示出更高的保守性和更低的GC含量。在一起，我们对组蛋白修饰的变化进行了系统分析，并展示了如何识别表观遗传和遗传调控的基因组区域特异性元件以及跨不同细胞类型的组蛋白修饰模式。我们发现k-mer序列组成的频率是组蛋白修饰模式的预测，表明一级DNA序列与细胞类型之间的组蛋白修饰变化相关。另外，谱系特异性的组蛋白修饰基因显示出更高的保守性和更低的GC含量。在一起，我们对组蛋白修饰的变化进行了系统分析，并展示了如何识别表观遗传和遗传调控的基因组区域特异性元件以及跨不同细胞类型的组蛋白修饰模式。