Retinoic acid-response elements with a highly repetitive structure isolated by immuno-selection from genomic DNA.
In vitro binding sites of retinoic acid receptors (RARs) were isolated from mouse genomic DNA by immunoprecipitation of receptor/DNA complexes. PuG(G/T)TCA half-site motifs, which constitute RA-responsive elements (RAREs), were identified in the immuno-selected fragments (ISFs), some of which contained highly repetitive arrangements of this motif. Genomic Southern analysis of a number of ISFs showed them to be of a single or low copy number. Several, but not all, ISFs acted as ligand-dependent RAREs in transient transfection assays. Two ISFs with repetitive RARE motifs responded preferentially to 9-cis retinoic acid-liganded retinoid X receptor in the presence or absence of co-transfected RAR, while little activation was seen with RAR alone in the presence of either all-trans or 9-cis retinoic acid. Another ISF, containing consensus TATA and CAAT box motifs, was shown to have RA-inducible promoter activity. The results suggest a high degree of promiscuity in response element recognition by retinoid receptors.
Rudert
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F
Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, Faculté de Médecine, Strasbourg, France.
Gronemeyer
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H
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000235:genetics*; D015698:Genomic Library; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin; D004247:DNA