title: Molecular analysis of the human SLC13A4 sulfate transporter gene promoter.
abstract: The human solute linked carrier (SLC) 13A4 gene is primarily expressed in the placenta where it is proposed to mediate the transport of nutrient sulfate from mother to fetus. The molecular mechanisms involved in the regulation of SLC13A4 expression remain unknown. To investigate the regulation of SLC13A4 gene expression, we analysed the transcriptional activity of the human SLC13A4 5'-flanking region in the JEG-3 placental cell line using luciferase reporter assays. Basal transcriptional activity was identified in the region -57 to -192 nucleotides upstream of the SLC13A4 transcription initiation site. Mutational analysis of the minimal promoter region identified Nuclear factor Y (NFY), Specificity protein 1 (SP1) and Krüppel like factor 7 (KLF7) motifs which conferred positive transcriptional activity, as well as Zinc finger protein of the cerebellum 2 (ZIC2) and helix-loop-helix protein 1 (HEN1) motifs that repressed transcription. The conserved NFY, SP1, KLF7, ZIC2 and HEN1 motifs in the SLC13A4 promoter of placental species but not in non-placental species, suggests a potential role for these putative transcriptional factor binding motifs in the physiological control of SLC13A4 mRNA expression.
authors.affiliation: Mater Medical Research Institute, South Brisbane, Queensland, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Jefferis
authors.forename: J
authors.initials: J
authors.lastname: Rakoczy
authors.forename: D G
authors.initials: DG
authors.lastname: Simmons
authors.forename: P A
authors.initials: PA
authors.lastname: Dawson
mesh_terms: D024506:5' Flanking Region; D027321:Anion Transport Proteins / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D017124:Conserved Sequence; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D010802:Phylogeny; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000076988:Sulfate Transporters; D027981:Symporters / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D027321:Anion Transport Proteins; D012333:RNA, Messenger; C400428:SLC13A4 protein, human; D000076988:Sulfate Transporters; D027981:Symporters; D008156:Luciferases