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PMID: 2159384 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Jun-Fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene.

Cell ·Vol. 61 ·No. 3 ·1990-05-04 ·Pages 497-504

Schüle R, Umesono K, Mangelsdorf DJ, Bolado J, Pike JW, Evans RM

Abstract

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.

MeSH Terms
Animals Base Sequence Binding Sites Carrier Proteins/metabolism Cell Line Cholecalciferol/pharmacology Chromosome Deletion DNA-Binding Proteins/metabolism Genes Humans Molecular Sequence Data Mutation Osteocalcin/genetics Promoter Regions, Genetic/drug effects Protein-Tyrosine Kinases/metabolism Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun Receptors, Cell Surface/metabolism Receptors, Retinoic Acid Restriction Mapping Sequence Homology, Nucleic Acid Transcription Factors/metabolism Transcription, Genetic/drug effects Transfection Tretinoin/pharmacology
Chemicals
Carrier Proteins DNA-Binding Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun Receptors, Cell Surface Receptors, Retinoic Acid Transcription Factors Osteocalcin Cholecalciferol Tretinoin Protein-Tyrosine Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Schüle R
Howard Hughes Medical Institute, Salk Institute, La Jolla, California 92037.
Umesono K
Mangelsdorf D J
Bolado J
Pike J W
Evans R M
Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
Published
1990-05-04
Pages
497-504
Language
English
Region
United States
NLM ID
0413066
Subset
IM
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