Identification of natural monomeric response elements of the nuclear receptor RZR/ROR. They also bind COUP-TF homodimers.
The receptor RZR/ROR is an important member of the nuclear receptor superfamily and has recently been shown to be the nuclear receptor for the pineal gland hormone melatonin. RZR/ROR binds as a monomer to DNA, and the human 5-lipoxygenase gene has been identified as the first RZR/ROR/melatonin-responding gene. Another prominent nuclear receptor is COUP-TF, which binds as a dimer to DNA. In this study, the sequences of known promoter regions of genes that may be involved in the physiological action of melatonin have been screened for putative monomeric RZR/ROR response elements. The binding of RZR/ROR and COUP-TF was compared and quantified on a set of 12 putative response elements. Interestingly, COUP-TF homodimers were found to bind with high affinity to some of the monomeric RZR/ROR response elements. Four RZR/ROR response elements, found in the genes of the mouse bifunctional enzyme, the rat bone sialoprotein, mouse Purkinje cell protein 2, and human p21(WAF1/CIP1), were shown to be inducible by melatonin under conditions of low constitutive activity. Surprisingly, the constitutive activity of COUP-TF was also stimulated by an unknown serum compound. The novel Purkinje cell protein 2 and p21(WAF1/CIP1) RZR/ROR/melatonin-responding genes may be the key for understanding the role of RZR/RORalpha in the mouse mutation staggerer and the antiproliferative action of melatonin, respectively.
Schräder
M
M
Clinique de Dermatologie, Hôpital Cantonal Universitaire, CH-1211 Genève 14, Switzerland.
Danielsson
C
C
Wiesenberg
I
I
Carlberg
C
C
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D051838:COUP Transcription Factor I; D016384:Consensus Sequence; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004746:Enoyl-CoA Hydratase / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D007535:Isomerases / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D063994:Peroxisomal Bifunctional Enzyme; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D044094:Receptors, Melatonin; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012177:Retinol-Binding Proteins / Q000235:genetics; D054840:Retinol-Binding Proteins, Cellular; D012795:Sialoglycoproteins / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*
C493956:CDKN1A protein, human; D051838:COUP Transcription Factor I; C493957:Cdkn1a protein, mouse; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C546871:IBSP protein, human; C546872:Ibsp protein, mouse; C546873:Ibsp protein, rat; D058574:Integrin-Binding Sialoprotein; D009097:Multienzyme Complexes; C497589:NR2F1 protein, human; D009419:Nerve Tissue Proteins; C497590:Nr2f1 protein, mouse; C497591:Nr2f1 protein, rat; C518456:RBP1 protein, human; C518458:Rbp1 protein, rat; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D018168:Receptors, Retinoic Acid; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D012795:Sialoglycoproteins; D014157:Transcription Factors; C082925:retinoic acid receptor beta; D015094:3-Hydroxyacyl CoA Dehydrogenases; C576253:EHHADH protein, human; C576254:Ehhadh protein, mouse; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases