Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors

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 (McPh-erson 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 (Bam-forth 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).

Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors ↗ Stable identifier: R-HSA-8864260 The AP-2 (TFAP2) family of transcription factors includes five proteins in mammals: TFAP2A (AP-2 alpha), TFAP2B (AP-2 beta), TFAP2C (AP-2 gamma), TFAP2D (AP-2 delta) and TFAP2E (AP-2 epsilon). The AP-2 family transcription factors are evolutionarily conserved in metazoans and are characterized by a helix-span-helix motif at the C-terminus, a central basic region, and the transactivation domain at the Nterminus. The helix-span-helix motif and the basic region enable dimerization and DNA binding (Eckert et al. 2005).
TFAP2A and TFAP2C directly stimulate transcription of the estrogen receptor ESR1 gene (McPherson and Weigel 1999). TFAP2A expression correlates with ESR1 expression in breast cancer, and TFAP2C is frequently overexpressed in estrogen-positive breast cancer and endometrial cancer (deConinck et al. 1995, Turner et al. 1998. TFAP2A, TFAP2C, as well as TFAP2B can directly stimulate the expression of ERBB2, another important breast cancer gene (Bosher et al. 1996). Association of TFAP2A with the YY1 transcription factor significantly increases the ERBB2 transcription rate (Begon et al. 2005). In addition to ERBB2, the expression of another receptor tyrosine kinase, KIT, is also stimulated by TFAP2A and TFAP2B (Huang et al. 1998), while the expression of the VEGF receptor tyrosine kinase ligand VEGFA is repressed by TFAP2A (Ruiz et al. 2004, Li et al. 2012 TFAP2C plays a critical role in maintaining the luminal phenotype in human breast cancer and in influencing the luminal cell phenotype during normal mammary development (Cyr et al. 2015).
In placenta, TFAP2A and TFAP2C directly stimulate transcription of both subunits of the human chorionic gonadotropin, CGA and CGB (Johnson et al. 1997, LiCalsi et al. 2000. tion 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).   (Campillos et al. 2003).

Literature references
Followed by: TFAP2A in complex with DEK binds the APOE gene promoter

Literature references
Campillos, M., Valdivieso, F., Vázquez, J., García, MA. (2003). Transcriptional activation by AP-2alpha is modulated by the oncogene DEK.   TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation 10 DEK binds TFAP2A homodimers 11 TFAP2A in complex with DEK binds the APOE gene promoter 12 The APOE gene transcription is stimulated by the complex of TFAP2A homodimer and DEK 13 Negative regulation of activity of TFAP2 (AP-2) family transcription factors 14