DNA BENDING DETERMINES FOS-JUN HETERODIMER ORIENTATION

Heterodimeric transcription factors can bind to palindromic recognitio n elements in two opposite orientations with potentially distinct effe cts on transcriptional activity. We have determined the orientation of Fos-Jun binding at different AP-I sites using a novel gel-based fluor escence resonance energy transfer assay. The orientation preference of heterodimer binding varied over a greater than 10-fold range. Single base pair substitutions that alter bending of flanking sequences rever sed the orientation of heterodimer binding. Single amino acid substitu tions that reduce the difference in DNA bending between Fos and Jun al so reduced the orientation preference. Consequently, indirect read-out mediated by differences in DNA structure can contribute to the struct ural organization of nucleoprotein complexes.