The human transcription factor activation protein-2 gamma (AP-2gamma): gene structure, promoter, and expression in mammary carcinoma cell lines.
Human activation protein-2 gamma (hAP-2gamma) is a key developmental transcription factor. It has been implicated in mammary carcinogenesis through its regulation of HER-2/neu proto-oncogene and estrogen receptor gene The hAP-2gamma gene is located on human chromosome 20q13.2. We cloned this gene, deduced its genomic structure, and mapped and analyzed its promoter. The hAP-2gamma gene contains seven exons. Primer extension analysis and 5'-rapid amplification of complementary DNA ends studies show that there is a single transcription start site 232 nt upstream of the translational start codon. The promoter lacks canonical binding sites for basal transcription factors such as TATA and CCAAT boxes, but contains a cluster of CpG islands and may rely on an initiator element for transcription. Deletion analyses of the promoter and chloramphenicol acetyl transferase reporter gene assays indicate that the sequence between -746 and -575 is important for its expression in mammary carcinoma cell lines. The hAP-2gamma gene is marginally activated in these cells suggesting that increased transcription partly contributes to its abundance. Architecture of the gene and promoter strikingly resembles that of hAP-2alpha, which is located on a different chromosome, suggesting a cognate origin. hAP-2alpha and hAP-2gamma have some common and some distinct roles in cells, and are likely the remarkable results of gene duplication, translocation and functional divergence through evolution.
Li
Min
M
Rammelkamp Center for Education and Research, MetroHealth Campus, Case Western Reserve University, Cleveland, OH 44109, USA.
Wang
Yingqun
Y
Yu
Yihong
Y
Nishizawa
Mikio
M
Nakajima
Tatsuya
T
Ito
Seiji
S
Kannan
Perry
P
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes / Q000235:genetics; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics*; D024363:Transcription Initiation Site; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C493679:TFAP2C protein, human; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase