title: Identification and characterization of a versatile retinoid response element (retinoic acid receptor response element-retinoid X receptor response element) in the mouse tissue transglutaminase gene promoter.
abstract: Tissue transglutaminase (transglutaminase type II) is an intracellular protein cross-linking enzyme that accumulates in connective tissue and in cells undergoing apoptosis. Retinoids regulate the transcription of the mouse tissue transglutaminase gene via activation of regulatory elements contained within 4 kilobases of the 5'-end of the gene. Co-transfection studies with retinoid receptor expression vectors in CV-1 cells demonstrated that the mouse tissue transglutaminase promoter is activated by ligand activation of either retinoic acid receptor-retinoid X receptor (RAR.RXR) heterodimers or RXR homodimers. Optimal induction is achieved with retinoid receptor panagonists; partial activation can also be achieved with either RAR-specific or RXR-specific retinoids. Retinoid-dependent activation of the tissue transglutaminase promoter depends on both a proximal regulatory region containing sequences highly conserved between the human and the mouse tissue transglutaminase promoters and a distal region that includes a 30-base pair retinoid response element (mTGRRE1). mTGRRE1 contains three hexanucleotide half-sites (two canonical and one non-canonical) in a DR7/DR5 motif that bind both RAR*RXR heterodimers and RXR homodimers. These studies suggest that retinoid-dependent expression of the mouse tissue transglutaminase gene is mediated by a versatile tripartite retinoid response element located 1.7 kilobases upstream of the transcription start site.
authors.affiliation: Department of Pharmacology, University of Texas-Houston Medical School, 77225, USA.
authors.forename: L
authors.initials: L
authors.lastname: Nagy
authors.forename: M
authors.initials: M
authors.lastname: Saydak
authors.forename: N
authors.initials: N
authors.lastname: Shipley
authors.forename: S
authors.initials: S
authors.lastname: Lu
authors.forename: J P
authors.initials: JP
authors.lastname: Basilion
authors.forename: Z H
authors.initials: ZH
authors.lastname: Yan
authors.forename: P
authors.initials: P
authors.lastname: Syka
authors.forename: R A
authors.initials: RA
authors.lastname: Chandraratna
authors.forename: J P
authors.initials: JP
authors.lastname: Stein
authors.forename: R A
authors.initials: RA
authors.lastname: Heyman
authors.forename: P J
authors.initials: PJ
authors.lastname: Davies
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007438:Introns; D008156:Luciferases / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology*; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D011503:Transglutaminases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D008156:Luciferases; D015500:Chloramphenicol O-Acetyltransferase; D011503:Transglutaminases