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) (Gal beta4[Fuc alpha3]GlcNAc beta 3Gal b eta1,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 physiolo gical epitope of E-selectin. Since myeloglycan-type structure is also expre ssed in various types of human cancer and may mediate E-selectin-dependent metastasis, expression of FUTIV is oncodevelopmentally regulated. The mecha nisms controlling FUTIV expression remain to be clarified. In this report, we further characterize FUTIV gene structure and define a non-TATA box-depe ndent transcriptional start region just upstream from the translational sta rt. FUTIV promoter/reporter fusion constructs defined a "full-length" promo ter and highly active fragments in the macrophage-derived U937 and myeloid HL60 cell lines. One highly active fragment contains a consensus binding si te for the Ets-l transcription factor (Withers, D. A. and Hakomori, S. (199 7) Glycoconj. J. 14, 764). Gel shift analysis shows specific binding to thi s site in nuclear extracts from U937 cells. Mutation of the Ets consensus s ite significantly reduces FUTIV promoter activity in both cell lines. Gel s upershift and dominant negative cotransfection experiments identified the E ts family member Elk-l as one component binding and regulating the FUTIV pr omoter in U937 cells. The significance of FUTIV regulation by Elk-l is disc ussed.