Chapter 9 Molecular aspects of steroid receptor/DNA binding

Publisher Summary This chapter presents the molecular aspects of steroid receptor/DNA binding. The general principles used by transcription factors, and specifically steroid receptors, to accomplish the needed specificity and affinity for DNA is described in this chapter. Specific DNA binding by transcription factors forms the basis for the specificity of gene regulation. The molecular determinants for sequence specific DNA binding by proteins has been studied extensively using both structural and functional methods. Several general mechanisms determine both specificity and affinity of DNA binding, including interactions with the bases and phosphate backbone of the DNA, the role of DNA conformation and the oligomerization of the protein, as well as thermodynamic principles. Mutational and structural studies have shown that several mechanisms are involved in the discrimination process, including sequence specific base contacts, negative steric effects, and entropic driving forces. Thus, specificity within this group of receptors must be mediated at another level than DNA binding, possibly by differential transcription activity, as well as modulation by chromatin and other transcription factors.