Synergism of closely adjacent estrogen-responsive elements increases their regulatory potential

https://doi.org/10.1016/0022-2836(88)90635-3Get rights and content

Abstract

Recent gene transfer experiments have shown that an estrogen-responsive DNA element (ERE) GGTCANNNTGACC mediates the estrogen inducibility of the Xenopus laevis vitellogenin A1 and A2 genes as well as the chicken vitellogenin II gene. We report here on experiments that explain the estrogen regulation of the Xenopus vitellogenin B1 and B2 genes. In these genes, two ERE homologues, which have only low, if any, regulatory capacity on their own, act synergistically to achieve high estrogen inducibility. Furthermore we show that synergism of EREs is most efficient, when the two elements are closely adjacent and that it is lost when the synergistic elements are separated by 125 base-pairs. In-vitro estrogen receptor binding experiments indicate that co-operative binding of estrogen receptors to closely adjacent EREs is not essential for synergism of ERE homologues that have no intrinsic regulatory capacity. Functional synergism of EREs is observed in the human estrogen-responsive MCF-7 cell line as well as in mouse fibroblasts (Ltk) cotransfected with estrogen receptor expression vectors. Even expression of a truncated receptor protein lacking 178 amino acid residues of the ammo-terminal end allows synergism, suggesting that the amino-terminal end preceding the DNA-binding domain of the estrogen receptor is not required.

References (32)

  • E. Buetti et al.

    J. Mol. Biol

    (1986)
  • B. Groner et al.

    Biochim. Biophys. Acta

    (1984)
  • A. Hochschild et al.

    Cell

    (1986)
  • H.-M. Jantzen et al.

    Cell

    (1987)
  • L. Klein-Hitpaβ et al.

    Cell

    (1986)
  • V. Kumar et al.

    Cell

    (1987)
  • R. Miksicek et al.

    Cell

    (1986)
  • M. Pfahl

    Cell

    (1982)
  • M. Beato et al.
  • E.Y. Chen et al.

    DNA

    (1985)
  • L. Dente et al.

    Nucl. Acids Res

    (1983)
  • J.D. Dignam et al.

    Nucl. Acids Res

    (1981)
  • P.M. Drüge et al.

    Nucl. Acids Res

    (1986)
  • C.M. Gorman et al.

    Mol. Cell. Biol

    (1982)
  • S. Green et al.

    Nature (London)

    (1986)
  • A.D. Johnson et al.
  • Cited by (95)

    • Mechanistic insights into induction of vitellogenin gene expression by estrogens in Sydney rock oysters, Saccostrea glomerata

      2016, Aquatic Toxicology
      Citation Excerpt :

      In another study, ERα was shown to cooperatively bind to tandem half-EREs (in the presence of the coactivator protein GMGB1) and activate transcription driven by tandem half-EREs in a synergic manner (Joshi et al., 2011). These findings agree with the concept that closely spaced EREs tend to interact cooperatively as an estrogen response unit (ERU) and confer transcriptional synergism (Beekman et al., 1991; Klein-Hitpass et al., 1988). It is, therefore, tempting to speculate that the three half-EREs residing in the sgVtg promoter may interact and function in a similar fashion.

    • A distal estrogen responsive element upstream the cap site of human transthyretin gene is an enhancer-like element upon ERα and/or ERβ transactivation

      2013, Gene
      Citation Excerpt :

      Non-functional palindromic, half-palindromic and imperfect non-palindromic consensus ERE have been identified in several genes. Many of these elements are also functional and are responsible for gene responses to estrogen in an orientation- and distance-independent manner, acting as enhancers or silencers (Berry et al., 1989; Burt et al., 1989; Gaub et al., 1990; Klein-Hitpass et al., 1988a; Muller et al., 2009; Rishi et al., 1995; Seiler-Tuyns et al., 1986). There is also evidence that these functional elements, depending on their number of copies, spacing, distance and orientation may have different effects on the regulation of gene expression (Naar et al., 1991; Hyder et al., 2000; Klinge, 2001; Tyulmenkov and Klinge, 2001b).

    • Proteomic analysis of coregulators bound to ERα on DNA and Nucleosomes reveals coregulator dynamics

      2013, Molecular Cell
      Citation Excerpt :

      First, we tested how the number of EREs influenced CoR binding by incubating 1x, 2x, 3x, or 4x EREs immobilized on Dynabeads with HNE and E2-liganded ERα. Consistent with reports that more EREs create a transcriptional “synergistic” response (Klein-Hitpass et al., 1988), we found that four EREs promoted optimal binding of CBP, p300, SRCs, and subunits of the Mediator (MED) complex to E2-liganded ERα (see Figure S1A online; data not shown). We also tested whether a functional RNA Pol II promoter (from the Adenovirus E4 gene) fused to 4xEREs (referred to as 4xERE-E4) would further stabilize CoR complex formation, as it has been used widely in binding and in vitro transcription assays (Acevedo et al., 2004).

    • Control of vitellogenin genes expression by sequences derived from transposable elements in rainbow trout

      2010, Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
      Citation Excerpt :

      VTG are usually encoded by small multigene families which mostly form a vtg gene cluster in a conserved syntenic group [21]. The promoter structure of vtg genes is generally quite simple [15,16,19,22,23], consisting of a consensus or imperfect EREs plus additional enhancers located close to the transcriptional start site (TSS). In salmonids, two paralogous vtg gene clusters arose from an ancestral tetraploïdization, at the base of salmonid radiation.

    View all citing articles on Scopus

    This work was supported by the Deutsche Forschungsgemeinschaft (Ry 51–2).

    View full text