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Mol Cell Biol. Mar 1989; 9(3): 1376–1380.
PMCID: PMC362737

Fine mapping of a mouse metallothionein gene metal response element.

Abstract

Metal-regulated transcription of metallothionein (MT) genes in higher eucaryotes involves multiple copies of a highly conserved 17-base-pair metal-regulatory element (MRE). We have assayed by transient transfection the ability of mouse MT-I element d (MREd) to confer metal responsivity to constructs containing the mouse MT-I TATA box and the bacterial chloramphenicol acetyltransferase indicator gene. A single copy of MREd works bidirectionally to afford a three- to fourfold induction, and dual copies act cooperatively to yield a 10- to 20-fold response. Element d responds to the same spectrum of heavy metals as doses the complete MT gene promoter. The sequences involved in induction by metals were delineated by analyzing point mutations in MREd. While nucleotides of the highly conserved core sequence TGCPuCXC are critical, substitutions in the less conserved regions affect the induction response only marginally. These sequences include residues of a potential Sp1-binding site, suggesting that if Sp1 binds to MREd, it has little if any role in induction by metals.

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Selected References

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  • Andersen RD, Taplitz SJ, Wong S, Bristol G, Larkin B, Herschman HR. Metal-dependent binding of a factor in vivo to the metal-responsive elements of the metallothionein 1 gene promoter. Mol Cell Biol. 1987 Oct;7(10):3574–3581. [PMC free article] [PubMed]
  • Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. [PubMed]
  • Cao ZD, Barron EA, Carillo AJ, Sharp ZD. Reconstitution of cell-type-specific transcription of the rat prolactin gene in vitro. Mol Cell Biol. 1987 Oct;7(10):3402–3408. [PMC free article] [PubMed]
  • Carter AD, Felber BK, Walling MJ, Jubier MF, Schmidt CJ, Hamer DH. Duplicated heavy metal control sequences of the mouse metallothionein-I gene. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7392–7396. [PMC free article] [PubMed]
  • Carthew RW, Chodosh LA, Sharp PA. The major late transcription factor binds to and activates the mouse metallothionein I promoter. Genes Dev. 1987 Nov;1(9):973–980. [PubMed]
  • Fürst P, Hu S, Hackett R, Hamer D. Copper activates metallothionein gene transcription by altering the conformation of a specific DNA binding protein. Cell. 1988 Nov 18;55(4):705–717. [PubMed]
  • Hamer DH. Metallothionein. Annu Rev Biochem. 1986;55:913–951. [PubMed]
  • Imagawa M, Chiu R, Karin M. Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP. Cell. 1987 Oct 23;51(2):251–260. [PubMed]
  • Jones NC, Rigby PW, Ziff EB. Trans-acting protein factors and the regulation of eukaryotic transcription: lessons from studies on DNA tumor viruses. Genes Dev. 1988 Mar;2(3):267–281. [PubMed]
  • Karin M, Haslinger A, Holtgreve H, Cathala G, Slater E, Baxter JD. Activation of a heterologous promoter in response to dexamethasone and cadmium by metallothionein gene 5'-flanking DNA. Cell. 1984 Feb;36(2):371–379. [PubMed]
  • Karin M, Haslinger A, Holtgreve H, Richards RI, Krauter P, Westphal HM, Beato M. Characterization of DNA sequences through which cadmium and glucocorticoid hormones induce human metallothionein-IIA gene. Nature. 1984 Apr 5;308(5959):513–519. [PubMed]
  • Lee W, Haslinger A, Karin M, Tjian R. Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40. Nature. 1987 Jan 22;325(6102):368–372. [PubMed]
  • Mermod N, Williams TJ, Tjian R. Enhancer binding factors AP-4 and AP-1 act in concert to activate SV40 late transcription in vitro. Nature. 1988 Apr 7;332(6164):557–561. [PubMed]
  • Mueller PR, Salser SJ, Wold B. Constitutive and metal-inducible protein:DNA interactions at the mouse metallothionein I promoter examined by in vivo and in vitro footprinting. Genes Dev. 1988 Apr;2(4):412–427. [PubMed]
  • Pavlakis GN, Hamer DH. Regulation of a metallothionein-growth hormone hybrid gene in bovine papilloma virus. Proc Natl Acad Sci U S A. 1983 Jan;80(2):397–401. [PMC free article] [PubMed]
  • Richards RI, Heguy A, Karin M. Structural and functional analysis of the human metallothionein-IA gene: differential induction by metal ions and glucocorticoids. Cell. 1984 May;37(1):263–272. [PubMed]
  • Searle PF, Stuart GW, Palmiter RD. Metal regulatory elements of the mouse metallothionein-I gene. Experientia Suppl. 1987;52:407–414. [PubMed]
  • Seguin C, Hamer DH. Regulation in vitro of metallothionein gene binding factors. Science. 1987 Mar 13;235(4794):1383–1387. [PubMed]
  • Stuart GW, Searle PF, Chen HY, Brinster RL, Palmiter RD. A 12-base-pair DNA motif that is repeated several times in metallothionein gene promoters confers metal regulation to a heterologous gene. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7318–7322. [PMC free article] [PubMed]
  • Stuart GW, Searle PF, Palmiter RD. Identification of multiple metal regulatory elements in mouse metallothionein-I promoter by assaying synthetic sequences. Nature. 317(6040):828–831. [PubMed]
  • de Wet JR, Wood KV, DeLuca M, Helinski DR, Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. [PMC free article] [PubMed]

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