The metabolic, defensive, communicative and pathogenic capabilities of eubacteria depend on their repertoire of genes and ability to regulate the expression of them. Sigma and transcription factors have fundamental roles in controlling these processes. Here, we show that sigma, transcription factors (TFs) and the number of protein coding genes occur in different magnitudes across 291 non-redundant eubacterial genomes. We suggest that these differences can be explained based on the fact that the universe of TFs, in contrast to sigma factors, exhibits a greater flexibility for transcriptional regulation, due to their ability to sense diverse stimuli through a variety of ligand-binding domains by discriminating over longer regions on DNA, through their diverse DNA-binding domains, and by their combinatorial role with other sigmas and TFs. We also note that the diversity of extra-cytoplasmic sigma factors and TF families is constrained in larger genomes. Our results indicate that most widely distributed families across eubacteria are small in size, while large families are relatively limited in their distribution across genomes. Clustering of the distribution of transcription and sigma families across genomes suggests that functional constraints could force their co-evolution, as was observed in sigma54, IHF and EBP families. Our results also indicate that large families might be a consequence of lifestyle, as pathogens and free-living organisms were found to exhibit a major proportion of these expanded families. Our results suggest that understanding proteomes from an integrated perspective, as presented in this study, can be a general framework for uncovering the relationships between different classes of proteins.