Region-Specific Network Analysis Reveals That Epigenetic Modifications Outside Transcriptional Start Sites Are Tightly Linked to mRNA

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.