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.

[1]  K. Yamamoto,et al.  Hormone-mediated repression: a negative glucocorticoid response element from the bovine prolactin gene. , 1988, Genes & development.

[2]  B. Spiegelman,et al.  Common DNA binding site for Fos protein complexesand transcription factor AP-1 , 1988, Cell.

[3]  K. Yamamoto,et al.  DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo , 1983, Cell.

[4]  K. Yamamoto,et al.  Mutations in the glucocorticoid receptor zinc finger region that distinguish interdigitated DNA binding and transcriptional enhancement activities. , 1989, Genes & development.

[5]  E. Wagner,et al.  Differentiation of F9 teratocarcinoma stem cells after transfer of c-fos proto-oncogenes , 1984, Nature.

[6]  B. Franza,et al.  The Fos complex and Fos-related antigens recognize sequence elements that contain AP-1 binding sites. , 1988, Science.

[7]  B. Franza,et al.  Fos and Jun bind cooperatively to the AP-1 site: reconstitution in vitro. , 1988, Genes & development.

[8]  R. Tjian,et al.  Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. , 1987, Science.

[9]  H. Stunnenberg,et al.  Glucocorticoid receptor binds cooperatively to adjacent recognition sites. , 1989, The EMBO journal.

[10]  R. Tjian,et al.  Leucine repeats and an adjacent DNA binding domain mediate the formation of functional cFos-cJun heterodimers. , 1989, Science.

[11]  R. Palmiter,et al.  A 12-base-pair DNA motif that is repeated several times in metallothionein gene promoters confers metal regulation to a heterologous gene. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[12]  D. Kulesh,et al.  Activation of an intron enhancer within the keratin 18 gene by expression of c-fos and c-jun in undifferentiated F9 embryonal carcinoma cells. , 1990, Genes & development.

[13]  K. Yamamoto,et al.  Glucocorticoid receptor mutants that define a small region sufficient for enhancer activation. , 1987, Science.

[14]  K. Yamamoto,et al.  Signal transduction and transcriptional regulation by glucocorticoid receptor-LexA fusion proteins. , 1988, Science.

[15]  J. Hopper,et al.  Regulated overproduction of the GAL4 gene product greatly increases expression from galactose-inducible promoters on multi-copy expression vectors in yeast. , 1987, Gene.

[16]  M. Sleigh,et al.  A nonchromatographic assay for expression of the chloramphenicol acetyltransferase gene in eucaryotic cells. , 1986, Analytical biochemistry.

[17]  N. Benvenisty,et al.  Glucocorticoids control phosphoenolpyruvate carboxykinase gene expression in a tissue specific manner. , 1987, Nucleic acids research.

[18]  B. Moss,et al.  Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[19]  P. O’Farrell,et al.  Activation and repression of transcription by homoeodomain-containing proteins that bind a common site , 1988, Nature.

[20]  Gene regulation by steroid hormones , 1989, Cell.

[21]  S. J. Thurston,et al.  SV40 stimulates expression of the transacting factor Sp1 at the mRNA level. , 1990, Genes & development.

[22]  Michael E. Greenberg,et al.  c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities , 1988, Cell.

[23]  D. Linzer,et al.  Co-localization of elements required for phorbol ester stimulation and glucocorticoid repression of proliferin gene expression. , 1989, Genes & development.

[24]  R. Evans,et al.  Multiple and cooperative trans-activation domains of the human glucocorticoid receptor , 1988, Cell.

[25]  M. Levine,et al.  Transcriptional repression of eukaryotic promoters , 1989, Cell.

[26]  J D Baxter,et al.  Negative regulation by glucocorticoids through interference with a cAMP responsive enhancer. , 1988, Science.

[27]  P. Sorger,et al.  Trimerization of a yeast transcriptional activator via a coiled-coil motif , 1989, Cell.

[28]  J. Jost,et al.  Positive and negative regulatory elements of chicken vitellogenin II gene characterized by in vitro transcription competition assays in a homologous system. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[29]  J. Drouin,et al.  Pro‐opiomelanocortin gene: A model for negative regulation of transcription by glucocorticoids , 1987, Journal of cellular biochemistry.

[30]  A. Wynshaw-Boris,et al.  Characterization of the phosphoenolpyruvate carboxykinase (GTP) promoter-regulatory region. II. Identification of cAMP and glucocorticoid regulatory domains. , 1986, The Journal of biological chemistry.

[31]  R. Brent,et al.  A bacterial repressor protein or a yeast transcriptional terminator can block upstream activation of a yeast gene , 1984, Nature.

[32]  K. Yamamoto,et al.  The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain , 1988, Nature.

[33]  T. Hunter,et al.  The c-fos protein interacts with c-Jun AP-1 to stimulate transcription of AP-1 responsive genes , 1988, Cell.

[34]  K. Yamamoto,et al.  Steroid receptor regulated transcription of specific genes and gene networks. , 1985, Annual review of genetics.

[35]  Y. Nakabeppu,et al.  DNA binding activities of three murine Jun proteins: Stimulation by Fos , 1988, Cell.

[36]  K. Yamamoto,et al.  Intracellular receptor concentration limits glucocorticoid-dependent enhancer activity. , 1987, Molecular endocrinology.

[37]  I. Wilson,et al.  Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolution , 1981, Nature.

[38]  T. Curran,et al.  Isolation and characterization of the c-fos(rat) cDNA and analysis of post-translational modification in vitro. , 1987, Oncogene.

[39]  A. van der Eb,et al.  A new technique for the assay of infectivity of human adenovirus 5 DNA. , 1973, Virology.

[40]  R. Harrison,et al.  Characterization of a monoclonal antibody to the rat liver glucocorticoid receptor. , 1984, Endocrinology.

[41]  T. Lockett,et al.  Oncogene expression in differentiating F9 mouse embryonal carcinoma cells. , 1987, Experimental cell research.

[42]  R. Evans,et al.  The steroid and thyroid hormone receptor superfamily. , 1988, Science.

[43]  P. Vogt,et al.  v-jun encodes a nuclear protein with enhancer binding properties of AP-1 , 1988, Cell.

[44]  W. Biggs,et al.  A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence , 1989, Nature.