title: Isolation and genomic analysis of the rat polymeric immunoglobulin receptor gene terminal domain and transcriptional control region.
abstract: The polymeric immunoglobulin receptor (pIgR) transports IgA and IgM across secretory epithelial cells and is essential in external immunity maintenance. We report here the structural characterization of the single-copy rat gene distributed over 30 kb of chromosomal DNA and analysis of its transcriptional control region. RNA sequencing and genomic analysis show a 5' terminal region originates at a major (+1) and a minor site producing an unusual 124-bp nontranslated exon I separated from a small 96-bp initiator ATG coding exon II by a 7.5-kb intron. The pIgR 5' region comprises a structured promoter with abundant helix-loop-helix (bHLH) cis elements positioned within an equivalent internal -70, -290, -528, and three centered at -745. The three latter bHLH elements each occur within 30-bp repeats at -690 to -780. Transient expression assays show a 1.3-kb 5' region is sufficient to drive expression in rat primary hepatocyte monolayer cultures, transformed human hepatic (HepG2) cells, and a mammary epithelial tumor cell line MCF-7, but is inactive in the rodent fibroblast 3T3 cell line. A minimal transcriptional promoter domain was deduced from sequentially deleted vectors revealing a +40 to -922 sequence to be sufficient for full activity. Further deletions within this region yield incremental losses in cis activity, indicating that multiple subregions comprise an extended transcriptional control region.
authors.affiliation: VA Medical Center and Department of Medicine, University of California, San Francisco 94121, USA.
authors.forename: E
authors.initials: E
authors.lastname: Fodor
authors.forename: A
authors.initials: A
authors.lastname: Feren
authors.forename: A
authors.initials: A
authors.lastname: Jones
mesh_terms: D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics; D005796:Genes / Q000235:genetics; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D006801:Humans; D008099:Liver; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D019056:Receptors, Polymeric Immunoglobulin