Indirect readout of DNA sequence by proteins: the roles of DNA sequence-dependent intrinsic and extrinsic forces.

Publisher Summary This chapter discusses the recent insights into how DNA sequence affects DNA structure and how solvent-mediated alterations in DNA structure may play a role in gene regulation. The stability and sequence specificity of many protein–DNA complexes is remarkably dependent on the sequences of bases that are not in contact with protein. In indirect readout, the stability and specificity of a protein–DNA complex is regulated by the sequence of bases not in contact with the protein. These noncontacted bases can inhibit or prevent the contacted DNA from being properly juxtaposed with protein groups. DNA sequence-dependent differences in the structure and flexibility of noncontacted bases lead to alterations in the strength and ease of forming protein–DNA contacts. Hence, noncontacted bases affect protein–DNA complex formation via sequence-dependent differences in their structure and flexibility. The sequence dependence of the effect of salt on a protein's affinity for DNA implies that for a given regulatory protein, the genes it controls can be differentially regulated by changes in salt type and concentration. An increasing number of examples exist of gene regulatory proteins whose affinity for DNA-binding sites are dependent on cation composition. Thus, cations may have a larger role in differentially regulating gene expression than has thus far been recognized.