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 fu nction. 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 spec ies to bend DNA and the molecular mechanisms underlying this process. Diffe rential DNA bending is observed in yeast and plant MADS-box proteins. Like MEF2A, the yeast proteins Rlm1 and Smp1 exhibit low DNA bending propensitie s. A comparison of serum response factor and SQUA reveals that the basic me chanisms of DNA bending appear to be conserved between these proteins, alth ough several key differences do exist. In contrast to serum response factor , SQUA bends DNA in a DNA sequence-dependent manner. in both proteins, prot ein-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 o f DNA bending. However, although residues which are involved in DNA bending are predicted to be located in similar positions in their tertiary structu res, different residues dictate bending by each protein. Further complexiti es are uncovered in the links between the DNA bending propensity and the bi nding specificity. In combination with structural studies, our results prov ide a model to explain how differential bending by MADS-box proteins is ach ieved at the molecular level and provide insights into how this might affec t their biological function. (C) 1999 Academic Press.