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FIGURE 9-33 Cooperative binding of two unrelated transcription factors to neighboring sites in a composite control element. (a) By themselves, both monomeric NFAT and heterodimeric AP1 transcription factors have low affinity for their respective binding sites in the IL-2 promoter-proximal region. Protein-protein interactions between NFAT and AP1 add to the overall stability of the NFAT-AP1-DNA complex, so that the two proteins bind to the composite site cooperatively. (b) Cooperative DNA binding by dimeric SRF and monomeric SAP1 can occur when their binding sites are separated by 5–30 bp and when the SAP1 binding site is inverted because the domain of SAP1 that interacts with SRF is connected to the DNA-binding domain of SAP1 by a flexible linker region of the SAP1 polypeptide chain (dotted line).
[Part (a) data from L. Chen et al., 1998, Nature 392:42, PDB ID 1a02; part (b) data from M. Hassler and T. J. Richmond, 2001, EMBO J. 20:3018, PDB ID 1hbx.]