Linked equilibria in regulation of transcription initiation

Assembly of transcriptional regulatory complexes often involves multiple binding processes and these binding processes are frequently coupled to one another. Small molecule binding can promote or inhibit DNA-binding or protein-protein interactions. DNA binding may be coupled to protein association. Finally, proteins may bind cooperatively to multiple sites in a transcriptional regulatory region. The level of transcription initiation at a promoter reflects the assembly of regulatory complexes in a transcription control region. Quantitative mechanistic understanding of regulatory complex assembly requires dissection of the assembly process into its constituent interactions followed by measurements of linkage between the individual binding processes. Methods and approaches to achieving this quantitative understanding of transcription regulation are outlined in this chapter.