Molecular biologists construe signal transduction as a local process by which signaling molecules outside the cell interact with cellular receptors to initiate a cascade of biochemical reactions inside the cell, ultimately stimulating a protein “transcription factor” to activate gene expression (Figure 1). Transcription factors flag a particular stretch of DNA (the “coding region” of a gene) for transcription into RNA. Which genes can be activated by a given transcription factor is determined by the nucleotide sequence of the gene’s promoter – the stretch of DNA lying upstream of the coding region. For example, the transcription factor NF-κB binds to the nucleotide motif GGGACTTTCC, whereas CREB/ATF transcription factors target the motif TGACGTCA. These two transcription factors are activated by different receptor-mediated signal transduction pathways, providing distinct molecular channels by which extra-cellular events can regulate intracellular genomic response. The distribution of transcription factor-binding motifs across our ~22,000 gene promoters constitutes a “wiring diagram” that maps micro-environmental processes onto genome-wide transcriptional responses.
