MADS-box transcription factors adopt alternative mechanisms for bending DNA.

Transcription factor-induced DNA bending is important in determining local promoter architecture and it is thought to be a key determinant of their function. The human MADS-box transcription factors serum response factor and MEF2A exhibit different propensities to bend their binding sites. Here, we have investigated the ability of several family members from different species to bend DNA and the molecular mechanisms underlying this process. Differential DNA bending is observed in yeast and plant MADS-box proteins. Like MEF2A, the yeast proteins Rlm1 and Smp1 exhibit low DNA bending propensities. A comparison of serum response factor and SQUA reveals that the basic mechanisms of DNA bending appear to be conserved between these proteins, although several key differences do exist. In contrast to serum response factor, SQUA bends DNA in a DNA sequence-dependent manner. In both proteins, protein-DNA contacts made between residues in the beta-loop and the N-terminal end of the recognition helices in the MADS-box are the major determinants of DNA bending. However, although residues which are involved in DNA bending are predicted to be located in similar positions in their tertiary structures, different residues dictate bending by each protein. Further complexities are uncovered in the links between the DNA bending propensity and the binding specificity. In combination with structural studies, our results provide a model to explain how differential bending by MADS-box proteins is achieved at the molecular level and provide insights into how this might affect their biological function.