MethMotif.org 2023: The transcription factor binding motifs database that integrates cell-specific functions, co-factors and DNA methylation profiles.

Abstract

Motivation: Transcription factors binding events depend not only on a specific DNA motif but also on the chromatin context. To further explore this new transcriptional machinery level of complexity, we developed TFregulomeR, a MethMotif API R-library that facilitates batch queries. Our toolbox showed how the functions of TFs depend on cofactors, whose recruitment are also influenced by DNA methylation. This observation led us to release a new version of MethMotif that includes, in addition to more methyl-TF motifs and more organisms (Mus Musculus and Arabidopsis Thaliana), new features to discern context-specific TFs’ motifs associated with context-specific TFs' functions. Results: Using TFregulomeR, we expanded the range of information available in the new release of MethMotif by segregating TF’s binding motifs in the context of their cofactors and DNA methylation status. This strategy enabled us to build the first TF binding motifs database that incorporates context-specific position weight matrices coupled to epigenetic information and context-specific TFs’ function. Using this repository, we were able to further demonstrate that gene ontology (GO) enriched terms associated with transcription factor target genes may differ notably based on association with alternative cofactors and DNA methylation status. Conclusions: Overall, this update turns MethMotif into an integrative TF motif database with diverse regulatory element analysis tools accessible to a broad audience. Ultimately, this repository and its companion tools greatly facilitate the analysis of the consequences of epigenetic aberrations seen in diseases such as cancers. Availability: The MethMotif database is freely available at https://methmotif.org.