2000 , Volume 5, Special issue, p.100-111

Complexity of regulation of eukaryotic gene expression is mainly encoded in the structure of transcription regulatory regions of the genes by specific combinations of nucleotide motifs. These motifs compose targets for various transcription factors (TF), general and specific. We developed a method for recognition of such combinatorial structures referred as TF composite units in promoters of similarly regulated genes. TF composite unit consists of a binding site for a known transcription factor arranged with various flanking motifs - potential targets for additional transcription factors. Such TF composite units could serve as combinatory targets for complexes of different transcription factors synergistically regulating gene transcription. We found E2F composite units composed on E2F binding sites with additional flanking motifs in promoters of cell-cycle genes with maximal level of expression at the G1/S transition and in S phase. E2F composite units exhibit extremely high frequency and specific location in close proximity to the start of transcription in promoters of G1/S-phase specific genes in comparison with other promoters. Search for E2F composite units in genomic sequences provides possibility to identify new cell-cycle genes playing important role in the complex network of gene regulation controlling cell proliferation, differentiation and apoptosis.