TFAP2 homo- and heterodimers bind CITED and EP300/CREBBP

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).

CITED家族的转录共因子与转录因子TFAP2（AP-2）家族的螺旋跨螺旋（HSH）结构域相互作用，并募集转录共激活因子EP300（p300）和CREBBP（CBP）至TFAP2结合的DNA元件。CITED2对TFAP2蛋白的亲和力最高，其次为CITED4，而CITED1与TFAP2的相互作用亲和力极低。针对CITED蛋白的相互作用在TFAP2A（AP-2 alpha）、TFAP2B（AP2-beta）和TFAP2C（AP-2 gamma）中得到特异性验证，并基于序列相似性外推至TFAP2D（AP2-delta）和TFAP2E（AP-2 epsilon）（Braganca等，2002，Braganca等，2003）。CITED2基因缺陷的鼠胚胎表现出神经嵴缺陷、心脏畸形和肾上腺发育不全，这些缺陷至少部分可归因于Tfap2转录激活功能的缺陷（Bamforth等，2001）。