How transcription factors can adjust the gene expression floodgates.

The rate of transcription initiation is the main level of quantitative control of gene expression, primarily responsible for the accumulation of mRNAs in the cell. Many, if not all, molecular actors involved in transcription initiation are known but the mechanisms underlying the frequency of initiations, remain elusive. To make the connection between transcription factors and the frequency of transcription initiation, intricated aspects of this complex activity are classified i) depending on whether or not the DNA-bound transcription factors directly activate the commitment to transcription and ii) on the destructive or non-destructive effect of transcription initiation on the stability of promoter complexes. Two possible sources of synergy allowing the combinatorial specificity of transcription factors action are compared, for binding to DNA and for recruiting transcription machineries. Tentative formulations are proposed to discriminate the different micro-reversible modes of DNA binding cooperativity modulating the specificity and dosage of transcription initiation.