Transcription factor interactions: selectors of positive or negative regulation from a single DNA element.
The mechanism by which a single factor evokes opposite regulatory effects from a specific DNA sequence is not well understood. In this study, a 25-base pair element that resides upstream of the mouse proliferin gene was examined; it conferred on linked promoters either positive or negative glucocorticoid regulation, depending upon physiological context. This sequence, denoted a "composite" glucocorticoid response element (GRE), was bound selectively in vitro both by the glucocorticoid receptor and by c-Jun and c-Fos, components of the phorbol ester-activated AP-1 transcription factor. Indeed, c-Jun and c-Fos served as selectors of hormone responsiveness: the composite GRE was inactive in the absence of c-Jun, whereas it conferred a positive glucocorticoid effect in the presence of c-Jun, and a negative glucocorticoid effect in the presence of c-Jun and relatively high levels of c-Fos. The receptor also interacted selectively with c-Jun in vitro. A general model for composite GRE action is proposed that invokes both DNA binding and protein-protein interactions by receptor and nonreceptor factors.
Diamond
M I
MI
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
Miner
J N
JN
Yoshinaga
S K
SK
Yamamoto
K R
KR
D000818:Animals; D001483:Base Sequence; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D005938:Glucocorticoids / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011388:Prolactin; D011518:Proto-Oncogene Proteins / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C000634106:Prl2c2 protein, mouse; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D011388:Prolactin; D013755:Tetradecanoylphorbol Acetate