Human alpha (1,3)-fucosyltransferase IV (FUTIV) gene expression is regulated by elk-1 in the U937 cell line.
The alpha1,3-fucosyltransferase IV (FucTIV) encoded by its gene (FUTIV) is responsible for synthesis of Le(x) (Galbeta4[Fucalpha3]GlcNAcbeta3Galbeta1,R), which causes compaction in the morula stage of the preimplantation mouse embryo, as well as alpha1,3-fucosylation at multiple internal GlcNAc of unbranched poly-N-acetyllactosamine, termed "myeloglycan," the physiological epitope of E-selectin. Since myeloglycan-type structure is also expressed in various types of human cancer and may mediate E-selectin-dependent metastasis, expression of FUTIV is oncodevelopmentally regulated. The mechanisms controlling FUTIV expression remain to be clarified. In this report, we further characterize FUTIV gene structure and define a non-TATA box-dependent transcriptional start region just upstream from the translational start. FUTIV promoter/reporter fusion constructs defined a "full-length" promoter and highly active fragments in the macrophage-derived U937 and myeloid HL60 cell lines. One highly active fragment contains a consensus binding site for the Ets-1 transcription factor (Withers, D. A., and Hakomori, S. (1997) Glycoconj. J. 14, 764). Gel shift analysis shows specific binding to this site in nuclear extracts from U937 cells. Mutation of the Ets consensus site significantly reduces FUTIV promoter activity in both cell lines. Gel supershift and dominant negative cotransfection experiments identified the Ets family member Elk-1 as one component binding and regulating the FUTIV promoter in U937 cells. The significance of FUTIV regulation by Elk-1 is discussed.
Withers
D A
DA
Pacific Northwest Research Institute, Seattle, Washington 98122, USA. dwithers@pnri.org
Hakomori
S I
SI
D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005647:Fucosyltransferases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D014157:Transcription Factors; D020298:U937 Cells; D050807:ets-Domain Protein Elk-1
D017931:DNA Primers; D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase