PMID- 18274891 OWN - NLM STAT- MEDLINE DCOM- 20080624 LR - 20211020 IS - 0282-0080 (Print) IS - 0282-0080 (Linking) VI - 25 IP - 3 DP - 2008 Apr TI - Transcriptional regulation of the fucosyltransferase VI gene in hepatocellular carcinoma cells. PG - 225-35 LID - 10.1007/s10719-008-9114-z [doi] AB - The alpha1,3-fucosyltransferase VI (FUT VI) protein is a key enzyme for synthesis of sialyl Lewis X and Lewis X in epithelial cells. Despite its importance, how FUT VI expression is regulated has not previously been elucidated. In this work, we examined transcriptional regulation of the FUT VI gene in hepatocellular carcinoma HepG2 cells. 5'-Rapid amplification of cDNA ends analysis revealed transcription start sites of FUT VI in HepG2 cells at +65 and +278 nucleotides (nt) downstream of the position registered in the Data Base of Human Transcription Start Sites. We determined promoter regions for FUT VI in HepG2 cells using a luciferase reporter gene assay. The promoter activities of constructs located 5'-upstream of the transcription start site decreased when the -186 to -156 and -56 to -19 nt regions were deleted. Site-directed mutagenesis of these regions revealed that two hepatocyte nuclear factor-4 alpha (HNF-4 alpha) and one octamer binding transcription factor-1 (Oct-1) binding sites are essential for FUT VI transcription. Furthermore, transient over-expression of HNF-4 alpha but not Oct-1 enhanced both FUT VI promoter activities and FUT VI mRNA levels in HuH-7 cells. These results suggest that two defined regions in the 5'-flanking region of the FUT VI transcription start site are critical for FUT VI transcription in HepG2 cells. FAU - Higai, Koji AU - Higai K AD - Department of Clinical Chemistry, School of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba, 274-8510, Japan. koji@phar.toho-u.ac.jp FAU - Miyazaki, Noriko AU - Miyazaki N FAU - Azuma, Yutaro AU - Azuma Y FAU - Matsumoto, Kojiro AU - Matsumoto K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080215 PL - United States TA - Glycoconj J JT - Glycoconjugate journal JID - 8603310 RN - 0 (Cell Cycle Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (HNF4A protein, human) RN - 0 (Hepatocyte Nuclear Factor 4) RN - 0 (OCA-S protein, human) RN - 0 (Transcription Factors) RN - EC 2.4.1.- (Fucosyltransferases) RN - EC 2.4.1.65 (FUT6 protein, human) SB - IM MH - 5' Flanking Region/genetics MH - Carcinoma, Hepatocellular/enzymology/*genetics MH - Cell Cycle Proteins/genetics MH - Cell Line, Tumor MH - DNA-Binding Proteins/genetics MH - Fucosyltransferases/*genetics MH - Gene Deletion MH - *Gene Expression Regulation, Enzymologic MH - *Gene Expression Regulation, Neoplastic MH - Hepatocyte Nuclear Factor 4/genetics MH - Humans MH - Liver Neoplasms/enzymology/*genetics MH - Mutagenesis, Site-Directed MH - Promoter Regions, Genetic/genetics MH - Transcription Factors/genetics MH - Transcription, Genetic/*genetics EDAT- 2008/02/16 09:00 MHDA- 2008/06/25 09:00 CRDT- 2008/02/16 09:00 PHST- 2007/03/23 00:00 [received] PHST- 2008/01/23 00:00 [accepted] PHST- 2008/01/06 00:00 [revised] PHST- 2008/02/16 09:00 [pubmed] PHST- 2008/06/25 09:00 [medline] PHST- 2008/02/16 09:00 [entrez] AID - 10.1007/s10719-008-9114-z [doi] PST - ppublish SO - Glycoconj J. 2008 Apr;25(3):225-35. doi: 10.1007/s10719-008-9114-z. Epub 2008 Feb 15.