Abstract
While most data analysis of epigenetic modifications has focused on the transcriptional start site proximal region (TPR), the non-TPR has received less attention. The understanding of interaction relationships of epigenetic modifications and their effects is incomplete, especially for the non-TPR. To study the interaction relationships among epigenetic modifications within the TPR and non-TPR, we presented an original analysis framework, that is, the region-specific epigenetic interaction network, where each gene element was introduced as a new dimension that can be separately analyzed based on region-specific signals. We derived the epigenetic interaction network (EIN) based on the Pearson correlation coefficient and partial correlation coefficient. Our analysis of the data of CD4+ cells showed that the majority of edges relate to a small set of nodes in the identified EIN. Most strikingly, we found that modifications in the non-TPR, especially introns, exhibit frequent and important interactions and are closely linked to mRNA. Moreover, we found that epigenetic modifications exhibit more consistent behavior in different regions of genes. Finally, we showed that these modifications can be easily divided into three categories, namely, (i) the class of less interaction, (ii) the class of negative effect and (iii) the class of positive effect, where the last two classes perfectly match previous results. Our results provide a new perspective for exploring the functional mechanisms of epigenetic modification.
Highlights
Over the past decade, it has been demonstrated that epigenetic modifications, such as histone modifications and DNA methylation, exert effects on biological processes including replication, transcription, DNA repair, genomic imprinting, normal development and more [1]–[3]
To study the interaction relationships among epigenetic modifications within the transcriptional start site proximal region (TPR) and non-TPR of genes, we present an original analysis of the region-specific epigenetic interaction network, in which eight gene elements are independently analyzed depending on their region-specific modification signals
The positive epigenetic interaction network (EIN) consists of two components, where one has 4 vertexes and the other has 305 vertexes, while the negative EIN consists of one component with 249 vertexes and 60 isolated vertexes
Summary
It has been demonstrated that epigenetic modifications, such as histone modifications and DNA methylation, exert effects on biological processes including replication, transcription, DNA repair, genomic imprinting, normal development and more [1]–[3]. Histone acetylation is mainly associated with gene activation, whereas histone methylation is linked to both gene activation and gene repression. The enrichment of H3K9ac and H3K4me in gene promoters and CpG islands is associated with gene activation, while the depletion of H3K9me and H3K27me in CpG islands is associated with gene repression [5]. The different combinatorial patterns of histone modification have led to the ‘‘histone code’’. Despite the breadth of the published results, our understanding of the mechanisms of epigenetic modifications and their effects remains incomplete
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