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. The interaction with CITED proteins was specifically demonstrated for TFAP2A (AP-2 alpha), TFAP2B (AP2-beta) and TFAP2C (AP-2 gamma), and is extrapolated to TFAP2D (AP2-delta) and TFAP2E (AP-2 epsilon) based on sequence similarity (Braganca et al. 2002, Braganca et al. 2003). Mouse embryos defective for CITED2 exhibit neural crest defects, cardiac malformations and adrenal agenesis, which can at least in part be attributed to defective Tfap2 transactivation (Bamforth et al. 2001).