Revealing epigenetic patterns in gene regulation through integrative analysis of epigenetic interaction network.

Chromatin components and DNA methylation play important roles in regulation of gene expression in mammalian genomes. However, the mechanism underlying how they regulate gene transcription, independently or synergistically, remains largely unknown. We constructed an epigenetic interaction network (EIN) of chromatin components, DNA methylation and gene expression by combining partial correlation coefficient with Pearson correlation coefficient. In EIN, we identified nine direct factors for gene expression. They constitute three interaction modules which synergistically affect gene expression. We introduced a new combination strategy to test how these direct factors in each module regulate gene expression synergistically. We found two inter-attracted patterns and one inter-repulsed patterns among the three modules. Furthermore, we identified 22 indirect factors for gene expression which have effect on gene expression via direct factors. DNA methylation, for example, could regulate gene expression through H3K4me3 and Pol II. Our approach has the potential to help in uncovering inherent relationships between epigenetic factors and gene transcription and guiding experiment.