DNA bending by Fos-Jun and the orientation of heterodimer binding depend on the sequence of the AP-1 site

Abstract

Interactions among transcription factors that bind to separate promoter elements depend on distortion of DNA structure and the appropriate orientation of transcription factor binding to allow juxtaposition of complementary structural motifs. We show that Fos and Jun induce distinct DNA bends at different binding sites, and that heterodimers bind to AP-1 sites in a preferred orientation. Sequences on each side of the consensus AP-1 recognition element have independent effects on DNA bending. A single base pair substitution outside the sequences contacted in the X-ray crystal structure alters DNA bending. Substitution of sequences flanking the AP-1 site has converse effects on DNA bending in opposite directions, suggesting that the extent of DNA bending by Fos and Jun is determined in part by the anisotropic bendability of sequences flanking the AP-1 site. DNA bending by Fos and Jun, and the orientation of heterodimer binding are interrelated. Reversal of the orientation of heterodimer binding causes a shift in the direction of DNA bending. The preferred orientation of heterodimer binding is determined both by contacts between a conserved arginine in the basic region of Fos and the central asymmetric guanine as well as the structure of sequences flanking the AP-1 site. Consequently, the structural adaptability of the Fos-Jun-AP1 complex may contribute to its functional versatility at different promoters.