Modeling the relationship of epigenetic modifications to transcription factor binding

Abstract

Transcription factors (TFs) and epigenetic modifications play crucial roles in the regulation of gene expression, and correlations between the two types of factors have been discovered. However, methods for quantitatively studying the correlations remain limited. Here, we present a computational approach to systematically investigating how epigenetic changes in chromatin architectures or DNA sequences relate to TF binding. We implemented statistical analyses to illustrate that epigenetic modifications are predictive of TF binding affinities, without the need of sequence information. Intriguingly, by considering genome locations relative to transcription start sites (TSSs) or enhancer midpoints, our analyses show that different locations display various relationship patterns. For instance, H3K4me3, H3k9ac and H3k27ac contribute more in the regions near TSSs, whereas H3K4me1 and H3k79me2 dominate in the regions far from TSSs. DNA methylation plays relatively important roles when close to TSSs than in other regions. In addition, the results show that epigenetic modification models for the predictions of TF binding affinities are cell line-specific. Taken together, our study elucidates highly coordinated, but location- and cell type-specific relationships between epigenetic modifications and binding affinities of TFs.