In a thoughtful review article, Barolo and Psakony ask some big questions about how the seven main signaling pathways that regulate development produce diverse and specific patterns of gene expression. They discuss three basis regulatory properties that are shared by many pathways even though the properties are mediated by very different machinery in the cell. The first, which they call activator insufficiency, means that a signal pathway response element (SPRE) alone is insufficient to drive gene expression through enhancer module in vivo. This leads to a requirement for the second property, cooperative activation. Full expression of target genes usually requires the presence of other transcriptional activators that are often expressed in a particular location of a group of cells. The powerful cooperative activation by the combination of these local factors with signaling to SPREs is then held in check by the third basic phenomenon, default repression. This means that transcription is actively repressed in the absence of an activating signal. In fact, the repressor is sometimes the same signal-regulated transcription factor that promotes activation in the presence of a signal. Together, the three properties may account for the diverse regulatory patterns and for sharp boundaries between developing tissues where even adjoining cells may adopt distinct cell fates.
S. Barolo, J. W. Posakony, Three habits of highly effective signaling pathways: Principles of transcriptional control by developmental cell signaling. Genes Dev. 16, 1167-1181 (2002). [Full Text]