DNA BENDING BY FOS-JUN AND THE ORIENTATION OF HETERODIMER BINDING DEPEND ON THE SEQUENCE OF THE AP-1 SITE

Interactions among transcription factors that bind to separate promote r elements depend on distortion of DNA structure and the appropriate o rientation of transcription factor binding to allow juxtaposition of c omplementary structural motifs, We show that Fos and Jun induce distin ct DNA bends at different binding sites, and that heterodimers bind td AP-I sites in a preferred orientation, Sequences on each side of the consensus AP-1 recognition element have independent effects on DNA ben ding. A single base pair substitution outside the sequences contacted in the X-ray crystal structure alters DNA bending, Substitution of seq uences flanking the AP-1 site has converse effects on DNA bending in o pposite directions, suggesting that the extent of DNA bending by Fos a nd Jun is determined in part by the anisotropic bendability of sequenc es flanking the AP-1 site. DNA bending by Fos and Jun, and the orienta tion of heterodimer binding are interrelated, Reversal of the orientat ion of heterodimer binding causes a shift in the direction of DNA bend ing, The preferred orientation of heterodimer binding is determined bo th by contacts between a conserved arginine in the basic region of Fos and the central asymmetric guanine as well as the structure of sequen ces flanking the AP-1 site, Consequently, the structural adaptability of the Fos-Jun-AP1 complex may contribute to its functional versatilit y at different promoters.