title: Organic anion and cation transporters occur in pairs of similar and similarly expressed genes.
abstract: Organic anion and cation transporters (OATs, OCTs, OCTNs, and ORCTLs), transmembrane proteins essential to renal xenobiotic excretion, are encoded by a group of related genes. As yet there have been no studies of the transcriptional regulation of this important gene family. While such studies have traditionally been labor-intensive, comparative genomics approaches are now available that have proven reliable guides to critical regulatory elements. We report here the genomic sequencing of murine OAT1 (the cDNA of which was originally cloned by us as NKT) and OAT3 (Roct), and derivation of phylogenetic footprints (evolutionarily conserved non-coding sequences) by comparison to the human genome. We find binding sites within these footprints for several transcription factors implicated in kidney development, including PAX1, PBX, WT1, and HNF1. Additionally, we note that OATs and OCTs occur in the human and mouse genomes as tightly linked pairs (OAT1 and OAT3, UST3 and OAT5, OAT4 and URAT1/RST, OCT1 and 2, OCTN1 and 2, ORCTL3 and 4) that are also close phylogenetic relations, with Flipt1 and 2, and OAT2 the only unpaired family members. Finally, we find that pair-members have similar tissue distributions, suggesting that the pairing might exist to facilitate the co-regulation of the genes within each pair.
authors.affiliation: Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0693, USA.
authors.forename: Satish A
authors.initials: SA
authors.lastname: Eraly
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Hamilton
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Nigam
mesh_terms: D024506:5' Flanking Region; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002874:Chromosome Mapping; D018983:DNA Footprinting; D040461:Gene Components; D016678:Genome; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D027362:Organic Anion Transport Protein 1 / Q000235:genetics* / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics* / Q000378:metabolism; D027702:Organic Cation Transporter 1 / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D012333:RNA, Messenger / Q000096:biosynthesis; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D027702:Organic Cation Transporter 1; D012333:RNA, Messenger; C105033:Slc22a6 protein, mouse; D014157:Transcription Factors; C114338:organic anion transport protein 3