Deducing Causal Relationships among Different Histone Modifications, DNA Methylation and Gene Expression

Histone modifications and DNA methylation are two major epigenetic factors regulating gene expression. However, the mechanism in which DNA methylation and histone modifications co-regulate gene expression was little studied. In our study, classifications of DNA methylaion and gene expression showed the complicated relationship between gene expression and epigenetic factors. A Bayesian network was constructed by using the high-resolution maps of histone modifications, DNA methylation and gene expression in human CD4+ T cells to deduce causal and combinatorial relationships among them. PolII was found as the only direct regulator to gene expression, which was not found in prior studies. Our Bayesian network showed that epigenetic factors such as H3K4me3, H3K27me3 and DNA methylation are key regulators of gene expression, though indirectly. However they were considered to combinatorially stabilize the state and structure of chromatin.