The field of protein transcription regulators and their DNA sequence specificity has been the most rapidly expanding in the last few years. The concerted interplay of protein transcription factors on the regulatory regions of eukaryotic genes (promoters, enhancers, origins of replication, silencers, and matrix-attached regions) regulates transcription levels; the differential activity of genes during development and the cell cycle, between cell types, and in response to physiological stimuli results from interdigitation of regulatory circuits controlling transcription initiation, finely tuned by the relative amounts of protein factors synthesized in a cell type, their phosphorylation, isoforms within factor families, the way protein regulators are brought in contact with one another through the patchwork of their cognate sites on the regulatory regions of genes, and by regulation of their nuclear import. The varying affinity of the same factor for its cognate DNA in different promoters can also be modulated by the type of proteins it is brought into contact with, by one or more nucleotide changes in its binding sites among promoters, and by the chromatin structure. The classification of protein transcriptional regulators attempted here according to their DNA binding specificity into those that bind AT-, GC-, GA, TG-rich and mixed motif has one obvious advantage: different protein factors that bind to the same DNA sequence will be found within the same class. In addition, this classification has allowed us to discern a class of transcriptional regulators whose binding site consists of a GA-and a CT-rich moiety; no other two pairs of dinucleotides compose a major class of factor sites. Special tribute has been paid to each individual gene that is regulated by a given transcription factor.