Transcriptional gene regulation is mediated through the interactions of specific regulatory proteins, notably transcription factors (TFs), with cis-regulatory genomic elements, including promoters and enhancers (1). TFs are a broad class of proteins that regulate and mediate transcription; they can be classified as general TFs, sequence-specific DNA binding TFs, or transcriptional co-regulators (we refer the readers to (2) for more details). Within this report, we limit the application of the TF term to the subset that engages with DNA in a sequence-specific manner via DNA binding domains (DBDs) (1,2). The sequence-specific binding of TFs at cis-regulatory elements occurs at TF binding sites (TFBSs), delineated genomic regions that are typically 6–20 bp in length (3). TFs can be classified into structurally related families based on their DBDs. TFs with DBDs from the same structural family tend to recognise similar DNA sequence motifs, except for zinc finger proteins (4,5). Although several biochemical and genome-wide assays exist to assess TF-DNA affinities and detect TFBSs, these assays cannot be performed for all TFs in all cell types and biological conditions. Thus, computational approaches and models
