title: Transcriptional regulation of fucosyltransferase 1 gene expression in colon cancer cells.
abstract: The α 1,2-fucosyltransferase I (FUT1) enzyme is important for the biosynthesis of H antigens, Lewis B, and Lewis Y. In this study, we clarified the transcriptional regulation of FUT1 in the DLD-1 colon cancer cell line, which has high expression of Lewis B and Lewis Y antigens, expresses the FUT1 gene, and shows α 1,2-fucosyltransferase (FUT) activity. 5'-rapid amplification of cDNA ends revealed a FUT1 transcriptional start site -10 nucleotides upstream of the site registered at NM_000148 in the DataBase of Human Transcription Start Sites (DBTSS). Using the dual luciferase assay, FUT1 gene expression was shown to be regulated at the region -91 to -81 nt to the transcriptional start site, which contains the Elk-1 binding site. Site-directed mutagenesis of this region revealed the Elk-1 binding site to be essential for FUT1 transcription. Furthermore, transfection of the dominant negative Elk-1 gene, and the chromatin immunoprecipitation (CHIp) assay, supported Elk-1-dependent transcriptional regulation of FUT1 gene expression in DLD-1 cells. These results suggest that a defined region in the 5'-flanking region of FUT1 is critical for FUT1 transcription and that constitutive gene expression of FUT1 is regulated by Elk-1 in DLD-1 cells.
authors.affiliation: Department of Medical Biochemistry, Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Taniuchi
authors.forename: Koji
authors.initials: K
authors.lastname: Higai
authors.forename: Tomomi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Azuma
authors.forename: Kojiro
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics*; D004789:Enzyme Activation; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D014162:Transfection; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D005647:Fucosyltransferases; D007983:Lewis Blood Group Antigens; D050807:ets-Domain Protein Elk-1; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C494112:ELK1 protein, human; C094162:Lewis Y antigen