Functional trends in structural classes of the DNA binding domains of regulatory transcription factors

The DNA-binding domain (DBD) structure of a regulatory transcription factor (TF) is important in determining its DNA sequence specificity, but it is unclear whether a relationship exists between DBD structure and general TF biological function or regulatory mechanism. We observed moderate enrichment of functional annotation terms among TFs of the same structural class in Escherichia coli, Saccharomyces cerevisiae, Drosophila melanogaster, or Mus musculus, suggesting some preference for TFs of similar structures in the regulation of similar processes. In yeast, we also found trends among TF structural classes in phenomena including gene expression coherence, DNA binding site motif similarity, the general or specific nature of TFs' regulatory roles, and the position of a TF in a gene regulatory network. These results suggest that the biophysical constraints of different TF structural classes play a role in their gene regulatory mechanisms.