Skip to main content
Log in

The molecular basis for the role of zinc in developmental biology

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Zinc regulates the gene expression machinery. It affects the structure of chromatin, the template function of its DNA, the activity of numerous transcription factors and of RNA polymerases. Hence, it determines both the types of mRNA transcripts synthesized and the rate of transcription itself. Alterations in one or more of these zinc dependent processes have been proposed to account for the proliferative arrest and teratology induced by zinc deficiency. To examine this proposal, studies of zinc during X. laevis development have been initiated. The kinetics of X. laevis oocyte zinc uptake and storage and of zinc utilization during embryogenesis have been examined first. Vitellogenin carries zinc into the oocyte. Ten % of the total zinc (10 ng/egg) remains within the cytosol while 90% (90 ng/egg) is stored in the yolk platelets associated with lipovitellin. The cytosolic pool is the source of the zinc for all newly formed metalloproteins involved in embryo development. The yolk platelet zinc pool is stored for later use during early metamorphosis. It is now possible to examine zinc transfer to molecules, such as e.g. transcription factors, and the role of the metal in their function in development and organogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Vallee BL, Falchuk KH: The biochemical basis of zinc physiology. Physiol Rev 73: 79–111, 1993

    PubMed  Google Scholar 

  2. Keen CL, Hurley LS: Zinc and reproduction: Effects of deficiency on foetal and postnatal development. In: CF Mills (ed). Zinc in Human Biology, Springer-Verlag, London, pp 183–220, 1989

    Google Scholar 

  3. Vallee BL, Falchuk KH: Zinc and gene expresson. Philos Trans R Soc Lond B Biol SCI 294: 185–l97, 1981

    PubMed  Google Scholar 

  4. Falchuk KH: Zinc deficiency and the Euglena gracilis chromatin. In: A. S. Prasad (ed). Essential and Toxic Trace Elements in Human Health and Disease, New York: Liss, pp 75–91, 1988

    Google Scholar 

  5. Falchuk KH: Zinc in developmental biology: the role of metal dependent transcriptional regulation. In: A.S. Prasad (ed). Essential and Toxic Trace Elements in Human Health and Disease: An Update. New York: Liss, pp 91–111, 1993

    Google Scholar 

  6. Hanas JS, Hazuda D, Bogenhagen DF, Wu FY-H, Wu C-W: Xenopus transcription factor A requires zinc for binding to the 5S gene. J Biol Chem 258: 14120–14125, 1983

    PubMed  Google Scholar 

  7. Miller J, McLachlan AD, Klug A: Repetitive zinc binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J 4: 1609–1614, 1985

    PubMed  Google Scholar 

  8. Stankiewicz A, Falchuk KH, Vallee BL: Composition and structure of zinc deficient Euglena gracilis chromatin. Biochemistry 22: 5150–5156, 1983

    PubMed  Google Scholar 

  9. Mazus B, Falchuk KH, Vallee BL: Histone formation, gene expression and zinc deficiency in Euglena gracilis. Biochemistry 23: 42–44, 1984

    PubMed  Google Scholar 

  10. Czupryn M, Falchuk KH, Vallee BL: Zinc deficiency and metabolism of histones and nonhistone proteins in Euglena gracilis. Biochemistry 26: 8263–8269, 1987

    Google Scholar 

  11. Castro CE, Alvares OF, Sevall JS: Diet-mediated alteration of chromatin structure. Federation Proc 45; 2394–2398, 1986

    Google Scholar 

  12. Castro CE, Alvares OF, Seval JS: Zinc deficiency decreases histone H1* in rat liver. Nutr Rep Int 34: 67–75, 1986

    Google Scholar 

  13. Falchuk KH, Gordon PR, Stankiewicz A, Hilt KL, Vallee BL: The E. Gracilis chromatin: A comparison of the effects of zinc-, iron-, magnesium-, or manganese-deficiency and cold shock. Biochemistry 25: 5388–5391, 1986

    PubMed  Google Scholar 

  14. Falchuk KH, Fawcett D, Vallee BL: Role of zinc in cell division of Euglena gracilis. J Cell Sci 17: 57–68, 1975

    PubMed  Google Scholar 

  15. Falchuk KH, Krisham A, Vallee BL: DNA distribution in the cell cycle of Euglena gracilis: Cytofluorometry of zinc deficient cells. Biochemistry 14: 3439–3444, 1975b

    PubMed  Google Scholar 

  16. Wackei WEC: Nucleic acids and metals III. Changes in nucleic acids, protein and metal content as a consequence of zinc deficiency in Euglena gracilis. Biochemistry 1: 859–865, 1962

    PubMed  Google Scholar 

  17. Crossley LL, Falchuk KH, Vallee BL: Messenger ribonucleic acid function and protein synthesis in zinc deficient E. gracilis. Biochemistry 21: 5359–5363, 1982

    PubMed  Google Scholar 

  18. Falchuk KH, Mazus B, Ber E, Ulpino-Lobb L, Vallee BL: Zinc deficiency and the Euglena gracilis chromatin: Formation of an alpha-amanitinresistant RNA polymerase II. Biochemistry 24: 2576–2580, 1985

    PubMed  Google Scholar 

  19. Freedman LP, Luisi BF, Korszun ZR, Basavappa R, Sigler PB, Yamamoto KR: The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain. Nature Lond 334: 543–546, 1988

    PubMed  Google Scholar 

  20. Schwabe JWR, Neuhaus D, Rhodes D: Solution structure of the DNAbinding domain of the oestrogen receptor. Nature Lond 348: 458–460, 1990

    PubMed  Google Scholar 

  21. Pan T, Coleman JE: GAL4 transciption factor is not a 'zinc finger' but forms a Zn(II)2Cys6 binuclear cluster. Proc Natl Acad Sci USA 87: 2977–2981, 1990

    Google Scholar 

  22. Frankel AD, Chen L, Cotter RJ, Pabo CO: Tat protein from human immunodeficiency virus forms a metal-linked dimer. Science Wash DC 240: 70–73, 1988

    Google Scholar 

  23. Sequeval D, Felenbok B: Relationship between zinc content and DNAbinding activity of the DNA-binding motif of the transcription factor ALCR in Aspergillus nidulans. Mol Gen Genet 242: 33–39, 1994

    PubMed  Google Scholar 

  24. Timmerman JE, Guiard B, Shechter E, Delsuc MA, Lallemand JY, Gervais M: The DNA-binding domain of the yeast Saccharomyces cervisiae CYP1(HAP1) transcription factor possesses two zinc ions which are complexed in a zinc cluster. Eur J Biochem 225: 593–599, 1994

    PubMed  Google Scholar 

  25. Ball LJ, Diakun GP, Gadhavi PL, Young NA, Armstrong EM, Garner CD, Laue ED: Zinc coordination in the DNA-binding domain of the yeast transcription activator PPR1. FEBS Lett 358: 278–282, 1995

    PubMed  Google Scholar 

  26. Li PM, Reichert J, Freyd G, Horvitz HR, Walsh CT: The LIM region of a presumptive Caenorhabditis elegans transcription factor is an iron-sulfur and zinc containing metallodomain. Proc Natl Acad Sci USA 88: 9210–9213, 1991

    PubMed  Google Scholar 

  27. Archer VE, Breton J, Sanchez-Garcia I, Osada H, Forster A, Thomson AJ, Rabbitts TH: Cysteine-rich LIM domains of Lim-homeodomain and LIM-only proteins contain zinc but not iron. Proc Natl Acad Sci USA 91: 316–320, 1994

    PubMed  Google Scholar 

  28. Kuwahara J, Coleman JE: Role of zinc (II) ions in the structure of the three-finger DNA binding domain of the SP1 transcription factor. Biochemistry 29: 8628–8631, 1990

    Google Scholar 

  29. Halvorsen YC, Nandabaln K, Dickson RC: LAC 9 DNA-binding domain coordinates two zinc atoms per monomer and contacts DNA as a dimer. J Biol Chem 265: 13283–13289, 1990

    PubMed  Google Scholar 

  30. Falchuk KH: Transcription factors in cellular differentiation and organogenesis. J Trace Elem Exp Med (in press)

  31. Liao X, Clemens KR, Tennant PE, Wright JM, Gottesfeld M: Specific interaction of the first three zinc fingers of TFIIIA with the internal control region of the Xenopus 5S RNA gene. J Mol Biol 223: 857, 1992

    PubMed  Google Scholar 

  32. Pan T, Freedman LP, Coleman JE: Cadmium-113 NMR studies of the DNA binding domain of the mammalian glucocorticoid receptor. Biochemistry 29: 9218–9225, 1990

    PubMed  Google Scholar 

  33. Johnston M: Genetic evidence that zinc is an essential cofactor in the DNA binding domain of GAL4 protein. Nature Lond 328: 353–355, 1987

    PubMed  Google Scholar 

  34. Kagi JHR, Kojima Y: Nomenclature of metallothionein. Experientia Suppl Basel 52: 19–22, 1987

    Google Scholar 

  35. Vallee BL, Coleman JE, Auld DS: Zinc fingers, zinc clusters, and zinc twists in DNA-binding protein domains. Proc Natl Acad Sci USA 88: 999–1003, 1991

    PubMed  Google Scholar 

  36. Schwabe JWR, Klug A: Zinc mining for protein domains. Nature Struct Biol 1: 345–349, 1994

    PubMed  Google Scholar 

  37. Eisen A, Taylor WE, Blumberg H, Young ET: The yeast regulatory protein ADR1 binds in a zinc dependent manner to the upstream activating sequence of ADH2. Cell Biol 8: 4552–4556, 1988

    Google Scholar 

  38. Colvard DS, Wilson EM: Zinc potentiation of androgen receptor binding to nuclei in vitro. Biochemistry 23: 3471–3478, 1984

    PubMed  Google Scholar 

  39. Seguin CA: Nuclear factor requires Zn2+ to bind a regulatory MRE element of the mouse gene encoding metallothionein-1. Gene 97: 295–300, 1991.

    PubMed  Google Scholar 

  40. Searle, PF: Zinc dependent binding of a liver nuclear factor to metal response element MRE-a of the mouse metallothionein gene and variant sequences. Nucleic Acid Res 18: 4683–4690, 1990

    PubMed  Google Scholar 

  41. Dailey L, Boseman-Roberts S, Heintz N: RNA polymerase II transcription factors H4TF-1 and H4TF-2 require metal to bind specific DNA sequences. Mol Cell Biol 7: 4582–4584, 1987

    PubMed  Google Scholar 

  42. Dailey L, Hanly SM, Roeder RG, Hinotz N: Distinct transcription factors bind specifically to two regions of the human histone 4 promotor. Proc Natl Acad Sci USA 83: 7241–7245, 1986

    PubMed  Google Scholar 

  43. Roark M, Sturtevant MA, Emery J, Vaessin H, Grell E, Bier E: scratch, a pan-neural gene encoding a zinc finger protein related to snail, promotes neuronal development. Genes Dev 9: 2384–2390, 1995

    PubMed  Google Scholar 

  44. Mellerick DM, Kassis JA, Zhang SD, Odenwald WF: castor encodes a novel zinc finger protein required for the development of a subset of CNS neurons in Drosophila. Neuron 9: 789–803, 1992

    PubMed  Google Scholar 

  45. Kuhnlein RP, Frommer G, Friedrich M, Gonzalez-Gaitan M, Weber A, Wagner-Bernholz JF, Gehring WJ, Jackle H, Schuh R: spalt encodes an evolutionary conserved zinc finger protein of novel structure which provides homeotic gene function in the head and tail region of the Drosophila embryo. EMBO J 13: 168–179, 1994

    PubMed  Google Scholar 

  46. Swiatek PJ, Gridely T: Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20. Genes Dev 7: 2071–2084, 1993

    PubMed  Google Scholar 

  47. Bernard O, Ganiatisas S, Kannourakis G, Dringer R: Kiz1, a protein with LIM zinc finger and kinase domains, is expressed mainly in neurons. Cell Growth Differ 5: 1159–1171, 1994

    PubMed  Google Scholar 

  48. Schutz B, Niessing J: Cloning and structure of a chicken zinc finger cDNA: Restricted expression in developing neural crest cells. Gene 148: 227–236, 1994

    PubMed  Google Scholar 

  49. Nagai T, Aruga J, Takada S, Gunther T, Sporle R, Schugart K, Mikoshiba K: The expression of the mouse Zicl, Zic2 and Zic3 gene suggests an essential role for Zic genes in body pattern formation. Dev Biol 182: 299–313, 1997

    PubMed  Google Scholar 

  50. Kostich WA, Sanes JR: Expression of zfh-4, a new member of the zinc finger-homeodomain family, in developing brain and muscles. Dev Dyn 202: 145–152, 1995

    PubMed  Google Scholar 

  51. Mevel-Ninio M, Terracol R, Kafatos FC: The ovo gene of Drosophila encodes a zinc finger protein required for female germ line development. EMBO J 10: 2259–2266, 1991

    PubMed  Google Scholar 

  52. Redemann N, Gaul U, Jackle H: Disruption of a putative Cys-zinc interaction eliminates the biological activity of the Krüppel finger protein. Nature Lond 332: 90–92, 1988

    PubMed  Google Scholar 

  53. Perrotti D, Melotti P, Skorski T, Casella I, Peschle C, Calabretta B: Overexpression of the zinc finger protein MZI inhibits hematopoietic development from embryonic stem cells: Correlation with negative regulation of CD34 and cmyc promoter activity. Mol Cell Biol 15: 6075–6087, 1995

    PubMed  Google Scholar 

  54. Krishnaraju K, Nguyen HQ, Liebermann DA, Hoffman B: The zinc finger transcription factor Egr-1 potentiates macrophage differentiation of hematopoietic cells. Mol Cell Biol 15: 5499–55–7, 1995

    Google Scholar 

  55. Hansen P, Riebessel M: The early development of Xenopus laevis. Springer-Verlag, Berlin, pp 1–18, 1991

    Google Scholar 

  56. Nomizu T, Falchuk KH, Vallee BL: Zinc, iron, and copper contents of Xenopus laevis oocytes and embryos. Mol Reprod Dev 36: 419, 1993

    PubMed  Google Scholar 

  57. Falchuk KH, Montorzi M, Vallee BL: Zinc uptake and distribution in Xenopus laevis oocytes and embryos. Biochemistry 34: 16524, 1995

    PubMed  Google Scholar 

  58. Montorsi M, Falchuk KH, Vallee BL: Vitellogenin and lipovitellin: Zinc proteins of Xenopus laevis oocytes. Biochemistry 34: 10851, 1995

    PubMed  Google Scholar 

  59. Jornvall H, Falchuk KH, Geraci G, Vallee BL: 1,10-phenanthroline and Xenopus laevis teratology. Biochem Biophys Res Comm 200: 1398, 1993

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Falchuk, K.H. The molecular basis for the role of zinc in developmental biology. Mol Cell Biochem 188, 41–48 (1998). https://doi.org/10.1023/A:1006808119862

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006808119862

Navigation