Jun-Fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene.
We present evidence that the vitamin D response element in the human osteocalcin gene confers responsiveness to the vitamin A metabolite, retinoic acid. Retinoic acid receptor (RAR) expressed in E. coli binds to this sequence in vitro. Transfection of RAR expression vectors in cultured cells activates heterologous promoters containing this sequence in vivo. This response element contains a consensus AP-1 site TGACTCA and in vitro is bound by the Jun-Fos complex. Unexpectedly, cotransfection of Jun and Fos expression vectors suppresses basal level transcription of the osteocalcin gene and suppresses induction by both retinoic acid and vitamin D3. Additional studies delimit an 11 nucleotide segment as a minimal hormone response element containing the AP-1 site as its core. These results indicate that two distinct classes of transcription factors can recognize common regulatory sequences, a phenomenon we refer to as cross-coupling.
Schüle
R
R
Howard Hughes Medical Institute, Salk Institute, La Jolla, California 92037.
Umesono
K
K
Mangelsdorf
D J
DJ
Bolado
J
J
Pike
J W
JW
Evans
R M
RM
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002762:Cholecalciferol / Q000494:pharmacology*; D002872:Chromosome Deletion; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015675:Osteocalcin / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018168:Receptors, Retinoic Acid; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors; D015675:Osteocalcin; D002762:Cholecalciferol; D014212:Tretinoin; D011505:Protein-Tyrosine Kinases