Abstract
The structure and organization of mouse hyaluronan synthase 1 gene, HAS1 were determined by direct sequencing of lambda phage clones carrying the entire gene and by application of the long and accurate (LA)-PCR method to amplify regions encompassing the exon-intron boundaries and all of the exons. This gene spans about 11kb of genomic DNA and consists of 5 exons and 4 introns. A similarity in the exon-intron organization was found between the genes of mouse HAS1 and Xenopus laevis DG42 which was recently identified as Xenopus hyaluronan synthase. The transcription initiation site was determined by rapid amplification of the cDNA ends (5'-RACE). Position +1 is located 55 nucleotides upstream of the ATG initiation codon. The promoter region of the HAS1 gene has no typical TATA box, but contains a CCAAT box located 190 nucleotides upstream of the transcription initiation site. Further analysis of 1.4 kb of the 5' flanking region revealed several potential binding motifs for transcription factors. This information about the gene structure may be useful for further studies on the promoter activity.
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- Campbell C., Quinn A. G., Ro Y. S., Angus B., Rees J. L. p53 mutations are common and early events that precede tumor invasion in squamous cell neoplasia of the skin. J Invest Dermatol. 1993 Jun;100(6):746–748. doi: 10.1111/1523-1747.ep12475717. [DOI] [PubMed] [Google Scholar]
- Connor F., Cary P. D., Read C. M., Preston N. S., Driscoll P. C., Denny P., Crane-Robinson C., Ashworth A. DNA binding and bending properties of the post-meiotically expressed Sry-related protein Sox-5. Nucleic Acids Res. 1994 Aug 25;22(16):3339–3346. doi: 10.1093/nar/22.16.3339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dailey L., Hanly S. M., Roeder R. G., Heintz N. Distinct transcription factors bind specifically to two regions of the human histone H4 promoter. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7241–7245. doi: 10.1073/pnas.83.19.7241. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeAngelis P. L., Achyuthan A. M. Yeast-derived recombinant DG42 protein of Xenopus can synthesize hyaluronan in vitro. J Biol Chem. 1996 Sep 27;271(39):23657–23660. doi: 10.1074/jbc.271.39.23657. [DOI] [PubMed] [Google Scholar]
- DeAngelis P. L., Papaconstantinou J., Weigel P. H. Molecular cloning, identification, and sequence of the hyaluronan synthase gene from group A Streptococcus pyogenes. J Biol Chem. 1993 Sep 15;268(26):19181–19184. [PubMed] [Google Scholar]
- Denny P., Swift S., Connor F., Ashworth A. An SRY-related gene expressed during spermatogenesis in the mouse encodes a sequence-specific DNA-binding protein. EMBO J. 1992 Oct;11(10):3705–3712. doi: 10.1002/j.1460-2075.1992.tb05455.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edwards J. B., Delort J., Mallet J. Oligodeoxyribonucleotide ligation to single-stranded cDNAs: a new tool for cloning 5' ends of mRNAs and for constructing cDNA libraries by in vitro amplification. Nucleic Acids Res. 1991 Oct 11;19(19):5227–5232. doi: 10.1093/nar/19.19.5227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster J. W., Dominguez-Steglich M. A., Guioli S., Kwok C., Weller P. A., Stevanović M., Weissenbach J., Mansour S., Young I. D., Goodfellow P. N. Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature. 1994 Dec 8;372(6506):525–530. doi: 10.1038/372525a0. [DOI] [PubMed] [Google Scholar]
- Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goa K. L., Benfield P. Hyaluronic acid. A review of its pharmacology and use as a surgical aid in ophthalmology, and its therapeutic potential in joint disease and wound healing. Drugs. 1994 Mar;47(3):536–566. doi: 10.2165/00003495-199447030-00009. [DOI] [PubMed] [Google Scholar]
- Gubbay J., Collignon J., Koopman P., Capel B., Economou A., Münsterberg A., Vivian N., Goodfellow P., Lovell-Badge R. A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature. 1990 Jul 19;346(6281):245–250. doi: 10.1038/346245a0. [DOI] [PubMed] [Google Scholar]
- Hall C. L., Turley E. A. Hyaluronan: RHAMM mediated cell locomotion and signaling in tumorigenesis. J Neurooncol. 1995 Dec;26(3):221–229. doi: 10.1007/BF01052625. [DOI] [PubMed] [Google Scholar]
- Hall C. L., Yang B., Yang X., Zhang S., Turley M., Samuel S., Lange L. A., Wang C., Curpen G. D., Savani R. C. Overexpression of the hyaluronan receptor RHAMM is transforming and is also required for H-ras transformation. Cell. 1995 Jul 14;82(1):19–26. doi: 10.1016/0092-8674(95)90048-9. [DOI] [PubMed] [Google Scholar]
- Harada H., Kitagawa M., Tanaka N., Yamamoto H., Harada K., Ishihara M., Taniguchi T. Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2. Science. 1993 Feb 12;259(5097):971–974. doi: 10.1126/science.8438157. [DOI] [PubMed] [Google Scholar]
- Imagawa M., Chiu R., Karin M. Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP. Cell. 1987 Oct 23;51(2):251–260. doi: 10.1016/0092-8674(87)90152-8. [DOI] [PubMed] [Google Scholar]
- Itano N., Kimata K. Expression cloning and molecular characterization of HAS protein, a eukaryotic hyaluronan synthase. J Biol Chem. 1996 Apr 26;271(17):9875–9878. doi: 10.1074/jbc.271.17.9875. [DOI] [PubMed] [Google Scholar]
- Itano N., Kimata K. Molecular cloning of human hyaluronan synthase. Biochem Biophys Res Commun. 1996 May 24;222(3):816–820. doi: 10.1006/bbrc.1996.0827. [DOI] [PubMed] [Google Scholar]
- Kimata K., Honma Y., Okayama M., Oguri K., Hozumi M., Suzuki S. Increased synthesis of hyaluronic acid by mouse mammary carcinoma cell variants with high metastatic potential. Cancer Res. 1983 Mar;43(3):1347–1354. [PubMed] [Google Scholar]
- Knudson W., Biswas C., Li X. Q., Nemec R. E., Toole B. P. The role and regulation of tumour-associated hyaluronan. Ciba Found Symp. 1989;143:150-9; discussion 159-69, 281-5. doi: 10.1002/9780470513774.ch10. [DOI] [PubMed] [Google Scholar]
- Lassar A. B., Buskin J. N., Lockshon D., Davis R. L., Apone S., Hauschka S. D., Weintraub H. MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer. Cell. 1989 Sep 8;58(5):823–831. doi: 10.1016/0092-8674(89)90935-5. [DOI] [PubMed] [Google Scholar]
- Laurent T. C., Fraser J. R. Hyaluronan. FASEB J. 1992 Apr;6(7):2397–2404. [PubMed] [Google Scholar]
- Lesley J., Hyman R., Kincade P. W. CD44 and its interaction with extracellular matrix. Adv Immunol. 1993;54:271–335. doi: 10.1016/s0065-2776(08)60537-4. [DOI] [PubMed] [Google Scholar]
- Levine A. J., Momand J., Finlay C. A. The p53 tumour suppressor gene. Nature. 1991 Jun 6;351(6326):453–456. doi: 10.1038/351453a0. [DOI] [PubMed] [Google Scholar]
- Meyer M. F., Kreil G. Cells expressing the DG42 gene from early Xenopus embryos synthesize hyaluronan. Proc Natl Acad Sci U S A. 1996 May 14;93(10):4543–4547. doi: 10.1073/pnas.93.10.4543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mukhopadhyay T., Roth J. A. Functional inactivation of p53 by antisense RNA induces invasive ability of lung carcinoma cells and downregulates cytokeratin synthesis. Anticancer Res. 1996 Jul-Aug;16(4A):1683–1689. [PubMed] [Google Scholar]
- Rosa F., Sargent T. D., Rebbert M. L., Michaels G. S., Jamrich M., Grunz H., Jonas E., Winkles J. A., Dawid I. B. Accumulation and decay of DG42 gene products follow a gradient pattern during Xenopus embryogenesis. Dev Biol. 1988 Sep;129(1):114–123. doi: 10.1016/0012-1606(88)90166-2. [DOI] [PubMed] [Google Scholar]
- Shapiro M. B., Senapathy P. RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res. 1987 Sep 11;15(17):7155–7174. doi: 10.1093/nar/15.17.7155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shyjan A. M., Heldin P., Butcher E. C., Yoshino T., Briskin M. J. Functional cloning of the cDNA for a human hyaluronan synthase. J Biol Chem. 1996 Sep 20;271(38):23395–23399. doi: 10.1074/jbc.271.38.23395. [DOI] [PubMed] [Google Scholar]
- Spicer A. P., Augustine M. L., McDonald J. A. Molecular cloning and characterization of a putative mouse hyaluronan synthase. J Biol Chem. 1996 Sep 20;271(38):23400–23406. doi: 10.1074/jbc.271.38.23400. [DOI] [PubMed] [Google Scholar]
- Spicer A. P., Olson J. S., McDonald J. A. Molecular cloning and characterization of a cDNA encoding the third putative mammalian hyaluronan synthase. J Biol Chem. 1997 Apr 4;272(14):8957–8961. doi: 10.1074/jbc.272.14.8957. [DOI] [PubMed] [Google Scholar]
- Tomida M., Koyama H., Ono T. Effects of adenosine 3':5'-cyclic monophosphate and serum on synthesis of hyaluronic acid in confluent rat fibroblasts. Biochem J. 1977 Mar 15;162(3):539–543. doi: 10.1042/bj1620539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsukiyama T., Becker P. B., Wu C. ATP-dependent nucleosome disruption at a heat-shock promoter mediated by binding of GAGA transcription factor. Nature. 1994 Feb 10;367(6463):525–532. doi: 10.1038/367525a0. [DOI] [PubMed] [Google Scholar]
- Turley E. A. The role of a cell-associated hyaluronan-binding protein in fibroblast behaviour. Ciba Found Symp. 1989;143:121-33; discussion 133-7, 281-5. doi: 10.1002/9780470513774.ch8. [DOI] [PubMed] [Google Scholar]
- Vogelstein B., Kinzler K. W. p53 function and dysfunction. Cell. 1992 Aug 21;70(4):523–526. doi: 10.1016/0092-8674(92)90421-8. [DOI] [PubMed] [Google Scholar]
- Watanabe K., Yamaguchi Y. Molecular identification of a putative human hyaluronan synthase. J Biol Chem. 1996 Sep 20;271(38):22945–22948. doi: 10.1074/jbc.271.38.22945. [DOI] [PubMed] [Google Scholar]
- Weigel P. H., Hascall V. C., Tammi M. Hyaluronan synthases. J Biol Chem. 1997 May 30;272(22):13997–14000. doi: 10.1074/jbc.272.22.13997. [DOI] [PubMed] [Google Scholar]
- Weintraub H., Tapscott S. J., Davis R. L., Thayer M. J., Adam M. A., Lassar A. B., Miller A. D. Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5434–5438. doi: 10.1073/pnas.86.14.5434. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williams T., Tjian R. Analysis of the DNA-binding and activation properties of the human transcription factor AP-2. Genes Dev. 1991 Apr;5(4):670–682. doi: 10.1101/gad.5.4.670. [DOI] [PubMed] [Google Scholar]
- Yamamoto K. K., Gonzalez G. A., Biggs W. H., 3rd, Montminy M. R. Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. Nature. 1988 Aug 11;334(6182):494–498. doi: 10.1038/334494a0. [DOI] [PubMed] [Google Scholar]
- Yim J. H., Wu S. J., Casey M. J., Norton J. A., Doherty G. M. IFN regulatory factor-1 gene transfer into an aggressive, nonimmunogenic sarcoma suppresses the malignant phenotype and enhances immunogenicity in syngeneic mice. J Immunol. 1997 Feb 1;158(3):1284–1292. [PubMed] [Google Scholar]
- Yoneda M., Yamagata M., Suzuki S., Kimata K. Hyaluronic acid modulates proliferation of mouse dermal fibroblasts in culture. J Cell Sci. 1988 Jun;90(Pt 2):265–273. doi: 10.1242/jcs.90.2.265. [DOI] [PubMed] [Google Scholar]