The helix-span-helix motif and the basic region of TFAP2 (AP-2) transcription factor family members TFAP2A, TFAP2B, TFAP2C, TFAP2D and TFAP2E enable dimerization and DNA binding. AP-2 dimers bind palindromic GC-rich DNA response elements that match the consensus sequence 5'-GCCNNNGGC-3' (Williams and Tjian 1991a, Williams and Tjian 1991b). Most of the AP-2 binding sites slightly differ from the consensus, and individual AP-2 family members may differ in their binding site preferences (McPherson and Weigel 1999, Orso et al. 2010). Transcriptional co-factors from the CITED family interact with the helix-span-helix (HSH) domain of TFAP2 (AP-2) family of transcription factors and recruit transcription co-activators EP300 (p300) and CREBBP (CBP) to TFAP2-bound DNA elements. CITED2 shows the highest affinity for TFAP2 proteins, followed by CITED4, while CITED1 interacts with TFAP2s with a very low affinity. Mouse embryos defective for CITED2 exhibit neural crest defects, cardiac malformations and adrenal agenesis, which can at least in part be attributed to a defective Tfap2 transactivation (Bamforth et al. 2001, Braganca et al. 2002, Braganca et al. 2003). DNA binding and transcriptional activity of TFAP2B homodimers is increased by binding to YEATS4 (GAS41) (Ding et al. 2006).