Finding de novo methylated DNA motifs

Abstract

Increasing evidence has shown that posttranslational modifications (PTMs) such as methylation and hydroxymethylation on cytosine would greatly impact the binding of transcription factors (TFs). However, there is a lack of motif finding algorithms with the function to search for motifs with PTMs. In this study, we expend on our previous motif finding pipeline Epigram to provide systematic de novo motif discovery and performance evaluation on methylated DNA motifs. Using the tool, we were able to identified methylated motifs in Arabidopsis DAP-seq data that were previously demonstrated to contain such motifs1. When applied to TF ChIP-seq and DNA methylome data in H1 and GM12878, our method successfully identified novel methylated motifs that can be recognized by the TFs or their co-factors. We also observed spacing constraint between the canonical motif of the TF and the newly discovered methylated motifs, which suggests operative recognition of these cis-elements by collaborative proteins.