Alternative titles; symbols
HGNC Approved Gene Symbol: TFAP2C
Cytogenetic location: 20q13.31 Genomic coordinates (GRCh38): 20:56,629,306-56,639,283 (from NCBI)
Families of related transcription factors are often expressed in the same cell lineages but at different times or sites in the developing embryo. The AP2 family appears to regulate the expression of genes required for development of tissues of ectodermal origin such as neural crest and skin (Williamson et al., 1996). AP2 may also be involved in the overexpression of c-erbB-2 (164870) in human breast cancer cells (Bosher et al., 1995).
Williamson et al. (1996) isolated an AP2-related cDNA. The predicted protein differs from AP2-alpha (107580) and -beta (601601) in the N-terminal activation domain, but is 75 to 85% conserved within the DNA-binding and dimerization domains. All 3 gene products (AP2-alpha, -beta, and -gamma) bind the GCCNNNGGC motif.
McPherson et al. (1997) purified the TFAP2C protein, which they designated ERF1, from an estrogen receptor (see 133430)-positive breast cancer cell line. Using peptide sequences to design primers, they cloned TFAP2C by PCR and conventional hybridization of a cDNA library developed from the same breast cancer cells. The deduced 450-amino acid protein has a calculated molecular mass of about 48 kD. TFAP2C and TFAP2A share 65% sequence identity overall and 76% identity in their C-terminal halves, which contain the DNA-binding and dimerization domains.
Li et al. (2002) detected expression of TFAP2C during pregnancy in chorion and, at lower levels, in decidua from 5 to 10 weeks of gestational age. They detected expression in placenta between weeks 16 and 40. Expression was similar to that of GCMA (603715), a chorion-specific transcription factor involved in the differentiation of trophoblasts in the placenta.
Williamson et al. (1996) obtained a genomic clone for TFAP2C. They showed it to have a similar gene structure to TFAP2A.
Li et al. (2002) determined that the TFAP2C gene contains 7 exons and spans about 8.4 kb. Exon 1 is untranslated. The promoter region of TFAP2C contains no canonical TATA and CCAAT boxes, but it does have a cluster of CpG islands, as well as binding sites for OCT1 (164175) and AP2.
Nakaki et al. (2013) showed that, without cytokines, simultaneous overexpression of 3 transcription factors, BLIMP1 (603423), PRDM14 (611781), and TFAP2C directs epiblast-like cells, but not embryonic stem cells, swiftly and efficiently into a primordial germ cell state. Notably, PRDM14 alone, but not BLIMP1 or TFAP2C, suffices for the induction of the primordial germ cell state in epiblast-like cells. The transcription factor-induced primordial germ cell state, irrespective of the transcription factors used, reconstitutes key transcriptome and epigenetic reprogramming in primordial germ cells, but bypasses a mesodermal program that accompanies primordial germ cell or primordial germ cell-like-cell specification by cytokines, including bone morphogenetic protein-4 (BMP4; 112262). Notably, the transcription factor-induced primordial germ cell-like cells contribute to spermatogenesis and fertile offspring.
By FISH, Williamson et al. (1996) mapped the TFAP2C gene to chromosome 20q13.2. A mouse genomic clone was used to map the mouse Tfap2c gene to chromosome 2H3-4.
Genevieve et al. (2005) reported 2 unrelated girls who presented with severe pre- and postnatal growth retardation and had de novo interstitial deletions of chromosome 20q13.2-q13.3. Molecular studies showed that the deletions were of paternal origin in both girls and were approximately 4.5 Mb in size, encompassing the GNAS imprinted locus (139320), including paternally imprinted Gnasxl, and the TFAP2C gene. Both patients had intractable feeding difficulties, microcephaly, facial dysmorphism with high forehead, broad nasal bridge, small chin and malformed ears, mild psychomotor retardation, and hypotonia. Genevieve et al. (2005) noted that a mouse model with disruption of the Gnasxl gene had poor postnatal growth and survival (Plagge et al., 2004), and that a patient reported by Aldred et al. (2002) with a paternal deletion of the GNAS complex also showed pre- and postnatal growth retardation and feeding difficulties. Moreover, disruption of the Tfap2c gene in mice has been shown to affect embryonic development (Werling and Schorle, 2002).
Werling and Schorle (2002) disrupted the Tfap2c gene in mice. Heterozygous mice were viable and fertile, but displayed reduced body size at birth. Homozygous mice were growth retarded and died at days 7 to 9 of embryonic development. Immunohistochemical analysis revealed that the trophectodermal cells that normally express Tfap2c failed to proliferate, resulting in absence of the labyrinth layer. As a consequence, the developing embryos suffered from malnutrition and died. Analysis of embryo cultures indicated that Tfap2c also regulates the expression of adenosine deaminase (ADA; 608958), a gene involved in purine metabolism that is expressed at the maternal-fetal interface. Werling and Schorle (2002) concluded that Tfap2c is required for early embryonic development and that it regulates genetic programs controlling the proliferation and differentiation of extraembryonic trophectodermal cells.
Aldred, M. A., Aftimos, S., Hall, C., Waters, K. S., Thakker, R. V., Trembath, R. C., Brueton, L. Constitutional deletion of chromosome 20q in two patients affected with Albright hereditary osteodystrophy. Am. J. Med. Genet. 113: 167-172, 2002. [PubMed: 12407707] [Full Text: https://doi.org/10.1002/ajmg.10751]
Bosher, J. M., Williams, T., Hurst, H. C. The developmentally regulated transcription factor AP-2 is involved in c-erbB-2 overexpression in human mammary carcinoma. Proc. Nat. Acad. Sci. 92: 744-747, 1995. [PubMed: 7846046] [Full Text: https://doi.org/10.1073/pnas.92.3.744]
Genevieve, D., Sanlaville, D., Faivre, L., Kottler, M.-L., Jambou, M., Gosset, P., Boustani-Samara, D., Pinto, G., Ozilou, C., Abeguile, G., Munnich, A., Romana, S., Raoul, O., Cormier-Daire, V., Vekemans, M. Paternal deletion of the GNAS imprinted locus (including Gnasxl) in two girls presenting with severe pre- and post-natal growth retardation and intractable feeding difficulties. Europ. J. Hum. Genet. 13: 1033-1039, 2005. [PubMed: 15915160] [Full Text: https://doi.org/10.1038/sj.ejhg.5201448]
Li, M., Wang, Y., Yu, Y., Nishizawa, M., Nakajima, T., Ito, S., Kannan, P. The human transcription factor activation protein-2 gamma (AP-2-gamma): gene structure, promoter, and expression in mammary carcinoma cell lines. Gene 301: 43-51, 2002. [PubMed: 12490322] [Full Text: https://doi.org/10.1016/s0378-1119(02)01057-0]
McPherson, L. A., Baichwal, V. R., Weigel, R. J. Identification of ERF-1 as a member of the AP2 transcription factor family. Proc. Nat. Acad. Sci. 94: 4342-4347, 1997. [PubMed: 9113991] [Full Text: https://doi.org/10.1073/pnas.94.9.4342]
Nakaki, F., Hayashi, K., Ohta, H., Kurimoto, K., Yabuta, Y., Saitou, M. Induction of mouse germ-cell fate by transcription factors in vitro. Nature 501: 222-226, 2013. [PubMed: 23913270] [Full Text: https://doi.org/10.1038/nature12417]
Plagge, A., Gordon, E., Dean, W., Boiani, R., Cinti, S., Peters, J., Kelsey, G. The imprinted signaling protein XL-alpha-s is required for postnatal adaptation to feeding. Nature Genet. 36: 818-826, 2004. [PubMed: 15273686] [Full Text: https://doi.org/10.1038/ng1397]
Werling, U., Schorle, H. Transcription factor gene AP-2-gamma essential for early murine development. Molec. Cell. Biol. 22: 3149-3156, 2002. [PubMed: 11940672] [Full Text: https://doi.org/10.1128/MCB.22.9.3149-3156.2002]
Williamson, J. A., Bosher, J. M., Skinner, A., Sheer, D., Williams, T., Hurst, H. C. Chromosomal mapping of the human and mouse homologues of two new members of the AP-2 family of transcription factors. Genomics 35: 262-264, 1996. [PubMed: 8661133] [Full Text: https://doi.org/10.1006/geno.1996.0351]