Human promoter genomic composition demonstrates non-random groupings that reflect general cellular function

Using ProSpector, a web-based promoter search and annotation tool, we have applied an unbiased approach to analyze the transcription factor binding site frequencies of 1400 base pair genomic segments positioned at 1200 base pairs upstream and 200 base pairs downstream of the transcriptional start site of 7298 commonly studied human genes. Partitional clustering of the transcription factor binding site composition within these promoter segments reveals a small number of gene groups that are selectively enriched for gene ontology terms consistent with distinct aspects of cellular function. Significance ranking of the class-determining transcription factor binding sites within these clusters show substantial overlap between the gene ontology terms of the transcriptions factors associated with the binding sites and the gene ontology terms of the regulated genes within each group.Thus, gene sorting by promoter composition alone produces partitions in which the "regulated" and the "regulators" cosegregate into similar functional classes. These findings demonstrate that the transcription factor binding site composition is non-randomly distributed between gene promoters in a manner that reflects and partially defines general gene class function.Amidst a continuous bombardment of diverse stimuli from the external environment, metazoan organisms have adopted multiple strategies to respond specifically and decisively to a myriad of extracellular events. The biological map that determines this is encoded within the gene regulatory regions of the genome. Deciphering the inherent language in these encrypted codes is a major challenge of the post-genomic era. The search, retrieval and examination of the upstream regulatory sequences of eukaryotic genes coupled with empirical determination of their transcriptional regulatory function has yielded a wealth of potentially useful information relevant to the sequence-specific codes used to dynamically coordinate the spatial, temporal, a