title: Identification of two regulatory elements controlling Fucosyltransferase 7 transcription in murine CD4+ T cells.
abstract: Fucosyltransferase VII encoded by the gene Fut7 is essential in CD4(+) T cells for the generation of E- and P-selectin ligands (E- and P-lig) which facilitate recruitment of lymphocytes into inflamed tissues and into the skin. This study aimed to identify regulatory elements controlling the inducible Fut7 expression in CD4(+) T cells that occurs upon activation and differentiation of naive T cells into effector cells. Comparative analysis of the histone modification pattern in non-hematopoetic cells and CD4(+) T cell subsets revealed a differential histone modification pattern within the Fut7 locus including a conserved non-coding sequence (CNS) identified by cross-species conservation comparison suggesting that regulatory elements are confined to this region. Cloning of the CNS located about 500 bp upstream of the Fut7 locus, into a luciferase reporter vector elicited reporter activity after transfection of the αβ-WT T cell line, but not after transfection of primary murine CD4(+) Th1 cells. As quantification of different Fut7 transcripts revealed a predominance of transcripts lacking the first exons in primary Th1 cells we searched for an alternative promoter. Cloning of an intragenic region spanning a 1kb region upstream of exon 4 into an enhancer-containing vector indeed elicited promoter activity. Interestingly, also the CNS enhanced activity of this intragenic minimal promoter in reporter assays in primary Th1 cells suggesting that both elements interact in primary CD4(+) T cells to induce Fut7 transcription.
authors.affiliation: Charité, Universitätsmedizin Berlin, Experimentelle Rheumatologie c/o. Deutsches Rheuma-Forschungszentrum, Charitèplatz 1, 10117 Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Pink
authors.affiliation: Charité, Universitätsmedizin Berlin, Experimentelle Rheumatologie c/o. Deutsches Rheuma-Forschungszentrum, Charitèplatz 1, 10117 Berlin, Germany.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Ratsch
authors.affiliation: Charité, Universitätsmedizin Berlin, Experimentelle Rheumatologie c/o. Deutsches Rheuma-Forschungszentrum, Charitèplatz 1, 10117 Berlin, Germany.
authors.forename: Maibritt
authors.initials: M
authors.lastname: Mardahl
authors.affiliation: Charité, Universitätsmedizin Berlin, Experimentelle Rheumatologie c/o. Deutsches Rheuma-Forschungszentrum, Charitèplatz 1, 10117 Berlin, Germany.
authors.forename: Micha F
authors.initials: MF
authors.lastname: Schröter
authors.affiliation: Charité, Universitätsmedizin Berlin, Experimentelle Rheumatologie c/o. Deutsches Rheuma-Forschungszentrum, Charitèplatz 1, 10117 Berlin, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Engelbert
authors.affiliation: Charité, Universitätsmedizin Berlin, Experimentelle Rheumatologie c/o. Deutsches Rheuma-Forschungszentrum, Charitèplatz 1, 10117 Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Triebus
authors.affiliation: Charité, Universitätsmedizin Berlin, Experimentelle Rheumatologie c/o. Deutsches Rheuma-Forschungszentrum, Charitèplatz 1, 10117 Berlin, Germany.
authors.forename: Alf
authors.initials: A
authors.lastname: Hamann
authors.affiliation: Charité, Universitätsmedizin Berlin, Experimentelle Rheumatologie c/o. Deutsches Rheuma-Forschungszentrum, Charitèplatz 1, 10117 Berlin, Germany; Charité, Universitätsmedizin Berlin, Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Hindenburgdamm 30, 12200 Berlin, Germany. Electronic address: uta.syrbe@charite.de.
authors.forename: Uta
authors.initials: U
authors.lastname: Syrbe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005647:Fucosyltransferases / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012045:Regulatory Sequences, Nucleic Acid; D018417:Th1 Cells / Q000378:metabolism
chemical_list: D005647:Fucosyltransferases; C514210:fucosyltransferase VII, mouse
keywords: Fucosyltransferase; Gene regulation; Immunology; Migration; T cell