Characterization of Korean Cattle Keratin IV Gene

  • Kim, D.Y. (Laboratory of Development & Differentiation, Korea Research Institute of Bioscience and Biotechnology) ;
  • Yu, S.L. (Laboratory of Development & Differentiation, Korea Research Institute of Bioscience and Biotechnology) ;
  • Sang, B.C. (Division of Animal Resources and Science, Chungnam National University) ;
  • Yu, D.Y. (Laboratory of Development & Differentiation, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2002.12.17
  • Accepted : 2003.03.17
  • Published : 2003.07.01


Keratins, the constituents of epithelial intermediate filaments, are precisely regulated in a tissue and development specific manner. There are two types of keratin in bovine. The type I is acidic keratin and the type II is neutral/basic keratin. 1.5 kb of 5' flanking sequence of Korean cattle Keratin IV gene, type II keratin (59 kDa), was cloned and sequenced. A symmetrical motif AApuCCAAA are located in a defined region upstream of the TATA box. Proximal SP1, AP1, E-box and CACC elements as the major determinants of transcription are identified. When it was compared to the bovine sequence from -600 bp to ATG upstream, the homology was 97% in nucleotide sequence. Several A and T sequences, located in the promoter region, are deleted in the Korean cattle. An expression vector consisted of Korean cattle Keratin IV gene promoter/SV40 large T antigen was transfected to HaCaT cell (Epithelial keratinocyte). The transformed HaCaT cells showed active proliferation when treated with PDGF (Platelet-derived growth factor) in 0.3% soft agar compared to control cells. These results indicate that Korean cattle Keratin IVgene promoter can be used as a promoter for transfection into epithelial cell.


Supported by : Functional Human Genome Project of Korea


  1. Eitan, S., S. Martin, P. Fabrice, B. Michelle and F. W. Erwin. 2000. The Mammalian UV respose: c-Jun induction is required for exit from p53-imposed growth arrest. Cell 103:897-907.
  2. Manfred, B., Z. Hanswalter and L. J. Jose. 1987. Differentially expressed bovine cytokeratin genes. Analysis of gene linkage and evolutionary conservation of 5'-upstream sequences. Embo. J. 6(3):567-575.
  3. Park, W. S., R. R. Oh, J. Y. Park, J. H. Lee, M. S. Shin, H. S. Kim, H. K. Lee, Y. S. Kim, S. Y. Kim, S. H. Lee, N. J. Yoo and J. Y. Lee. 2000. Somatic mutations of the trefoil factor family 1 gene in gastric cancer. Gastroenterology 119:691-698.
  4. Tinsley, J. M., C. Fisher and P. F. Searle. 1992. Abnormalities of epidermal differentiation associated with expression of the human papillomavirus type 1 early region in transgenic mice. J. Gen. Virol. 73:1251-1260.
  5. Sanger F., S. Nicklen and A. R. Coulson. 1977. DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. USA 74:5463-5467.
  6. Antonello, R., S. I. Jang, C. Roberta, M. S. Peter and G. M. Nedialka. 1998. Effect of AP1 Transcription factors on the regulation of transcription in normal human epidermal Keratinocytes. J. Invest. Dermatol. 110:34-40.
  7. Federio, C. M., H. Q. Mirian, M. M. Meytha and K. H. Walid. 1997. Cultivation, serial transfer, and differentiation of epidermal keratinocytes in serum-free medium. Biochem. Biophys. Res. Commun. 236:167-172..
  8. Peter, F. S., P. T. David, B. F. Karen and M. T. Jonathon. 1994. Stomach cancer in transgenic mice expressing human papillomaviurs type 16 early region genes from a keratin promoter. J. Gen. Virol. 75:1125-1137.
  9. Jone, T., E. Thomas, S. Georg, S. Axel et al. 2000. A transgenic mouse line that develops early-onset invasive gastric carcinoma provides a model for carcinoembryonic antigentargeted tumor therapy. Int. Journal of Cancer. 86:863-869.<863::AID-IJC16>3.0.CO;2-4
  10. Manfred, B., L. J. Jose and W. F. Werner. 1989. Enhancer elements directing cell-type-specific expression of cytokeratin genes and changes of the epithelial cytoskeleton by transfections of hybrid cytokeratin genes. Embo. J. 8(1):117-126.
  11. Alpana, G., T. Malati and P. D. Gupat. 1997. Differential reduction in the expression of keratin polypeptide in human gastric carcinomas. Cancer. Dete. Prev. 21(2):129-134.
  12. Jiang, C. K., H. S. Epstein, M. Tomic, I. M. Freedberg and M. Blumenberg. 1989. Epithelial-specific keratin gene expression: identification of a 300 base-pair controlling segment. Nuc. Acids. Res. 18(2):247-253.
  13. Oliver, G. O., D. J. Timothy and K. R. Anil. 1998. Transcription regulation of the differentiation-linked human K4 promoter is dependent upon esophageal-specific nuclear factors. J. Biol. Chem. 273(37):23912-23921.
  14. Tomohiko, A., N. Shinzaburo, I. Osamu et al. 1997. Detection of pancreatic and gastric cancer cells in peripheral and portal blood by amplification of keratin 19 mRNA with reverse transcriptase-polymerase chain reaction. Journal of Cancer 72:408-411.
  15. Seth, L. N., E. Winfried and D. J. Timothy. 1998. Mouse keratin 4 is necessary for internal epithelial integrity. J. Biol. Chem. 273(37):23904-23911.
  16. Angel, R., V. Miguel, B. Ana, L. Fernando and L. J. Jose. 1995. A 5'-upstream region of a bovine keratin 6 gene confers tissuespecific expression and hyperliferation-related induction in transgenic mice. Proc. Natl. Acad. Sci. USA. 92:4783-4787.
  17. Yeo, J. S., J. W. Kim, T. K. Chang, D. H. Nam, J. H. Han and C. B. Choi. 2002. Detection of DNA Fragment to Differentiate Korean Cattle. Asian-Aust. J. Anim. Sci. 15(8):1071-1075.