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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Nov 1;88(21):9563–9567. doi: 10.1073/pnas.88.21.9563

Characterization and mapping of human genes encoding zinc finger proteins.

P Bray 1, P Lichter 1, H J Thiesen 1, D C Ward 1, I B Dawid 1
PMCID: PMC52758  PMID: 1946370

Abstract

The zinc finger motif, exemplified by a segment of the Drosophila gap gene Krüppel, is a nucleic acid-binding domain present in many transcription factors. To investigate the gene family encoding this motif in the human genome, a placental genomic library was screened at moderate stringency with a degenerate oligodeoxynucleotide probe designed to hybridize to the His/Cys (H/C) link region between adjoining zinc fingers. Over 200 phage clones were obtained and are being sorted into groups by partial sequencing, cross-hybridization with oligodeoxynucleotide probes, and PCR amplification. Further, the genomic clones were cross-hybridized with a set of 30 zinc finger-encoding cDNAs (Kox1-Kox30) isolated from a human T-cell cDNA library. Four cDNAs (Kox4, Kox7, Kox12, and Kox15) were identified that match one or more genomic clones; these matches were confirmed by nucleotide sequence analysis. One or more clones from each locus were mapped onto human metaphase chromosomes by chromosomal in situ suppression hybridization with fluorescent probe detection. We mapped ZNF7/Kox4 to chromosome 8qter, ZNF19/Kox12 to 16q22, ZNF22/Kox15 to 10q11, and ZNF44/Kox7 to 16p11. The results of these analyses support the conclusion that the human genome contains many, probably several hundred, zinc finger genes with consensus H/C link regions.

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Selected References

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  1. Bellefroid E. J., Lecocq P. J., Benhida A., Poncelet D. A., Belayew A., Martial J. A. The human genome contains hundreds of genes coding for finger proteins of the Krüppel type. DNA. 1989 Jul-Aug;8(6):377–387. doi: 10.1089/dna.1.1989.8.377. [DOI] [PubMed] [Google Scholar]
  2. Bellefroid E. J., Poncelet D. A., Lecocq P. J., Revelant O., Martial J. A. The evolutionarily conserved Krüppel-associated box domain defines a subfamily of eukaryotic multifingered proteins. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3608–3612. doi: 10.1073/pnas.88.9.3608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown R. S., Sander C., Argos P. The primary structure of transcription factor TFIIIA has 12 consecutive repeats. FEBS Lett. 1985 Jul 8;186(2):271–274. doi: 10.1016/0014-5793(85)80723-7. [DOI] [PubMed] [Google Scholar]
  4. Call K. M., Glaser T., Ito C. Y., Buckler A. J., Pelletier J., Haber D. A., Rose E. A., Kral A., Yeger H., Lewis W. H. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell. 1990 Feb 9;60(3):509–520. doi: 10.1016/0092-8674(90)90601-a. [DOI] [PubMed] [Google Scholar]
  5. Chavrier P., Lemaire P., Revelant O., Bravo R., Charnay P. Characterization of a mouse multigene family that encodes zinc finger structures. Mol Cell Biol. 1988 Mar;8(3):1319–1326. doi: 10.1128/mcb.8.3.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chowdhury K., Deutsch U., Gruss P. A multigene family encoding several "finger" structures is present and differentially active in mammalian genomes. Cell. 1987 Mar 13;48(5):771–778. doi: 10.1016/0092-8674(87)90074-2. [DOI] [PubMed] [Google Scholar]
  7. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Devilee P., Thierry R. F., Kievits T., Kolluri R., Hopman A. H., Willard H. F., Pearson P. L., Cornelisse C. J. Detection of chromosome aneuploidy in interphase nuclei from human primary breast tumors using chromosome-specific repetitive DNA probes. Cancer Res. 1988 Oct 15;48(20):5825–5830. [PubMed] [Google Scholar]
  9. Fuscoe J. C., Collins C. C., Pinkel D., Gray J. W. An efficient method for selecting unique-sequence clones from DNA libraries and its application to fluorescent staining of human chromosome 21 using in situ hybridization. Genomics. 1989 Jul;5(1):100–109. doi: 10.1016/0888-7543(89)90092-x. [DOI] [PubMed] [Google Scholar]
  10. Greig G. M., England S. B., Bedford H. M., Willard H. F. Chromosome-specific alpha satellite DNA from the centromere of human chromosome 16. Am J Hum Genet. 1989 Dec;45(6):862–872. [PMC free article] [PubMed] [Google Scholar]
  11. Honda B. M., Roeder R. G. Association of a 5S gene transcription factor with 5S RNA and altered levels of the factor during cell differentiation. Cell. 1980 Nov;22(1 Pt 1):119–126. doi: 10.1016/0092-8674(80)90160-9. [DOI] [PubMed] [Google Scholar]
  12. Huebner K., Druck T., Croce C. M., Thiesen H. J. Twenty-seven nonoverlapping zinc finger cDNAs from human T cells map to nine different chromosomes with apparent clustering. Am J Hum Genet. 1991 Apr;48(4):726–740. [PMC free article] [PubMed] [Google Scholar]
  13. Kadonaga J. T., Carner K. R., Masiarz F. R., Tjian R. Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain. Cell. 1987 Dec 24;51(6):1079–1090. doi: 10.1016/0092-8674(87)90594-0. [DOI] [PubMed] [Google Scholar]
  14. Knöchel W., Pöting A., Köster M., el Baradi T., Nietfeld W., Bouwmeester T., Pieler T. Evolutionary conserved modules associated with zinc fingers in Xenopus laevis. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6097–6100. doi: 10.1073/pnas.86.16.6097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lania L., Donti E., Pannuti A., Pascucci A., Pengue G., Feliciello I., La Mantia G., Lanfrancone L., Pelicci P. G. cDNA isolation, expression analysis, and chromosomal localization of two human zinc finger genes. Genomics. 1990 Feb;6(2):333–340. doi: 10.1016/0888-7543(90)90574-e. [DOI] [PubMed] [Google Scholar]
  16. Lichter P., Boyle A. L., Cremer T., Ward D. C. Analysis of genes and chromosomes by nonisotopic in situ hybridization. Genet Anal Tech Appl. 1991 Feb;8(1):24–35. doi: 10.1016/1050-3862(91)90005-c. [DOI] [PubMed] [Google Scholar]
  17. Lichter P., Cremer T., Borden J., Manuelidis L., Ward D. C. Delineation of individual human chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries. Hum Genet. 1988 Nov;80(3):224–234. doi: 10.1007/BF01790090. [DOI] [PubMed] [Google Scholar]
  18. Lichter P., Tang C. J., Call K., Hermanson G., Evans G. A., Housman D., Ward D. C. High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science. 1990 Jan 5;247(4938):64–69. doi: 10.1126/science.2294592. [DOI] [PubMed] [Google Scholar]
  19. Manuelidis L., Ward D. C. Chromosomal and nuclear distribution of the HindIII 1.9-kb human DNA repeat segment. Chromosoma. 1984;91(1):28–38. doi: 10.1007/BF00286482. [DOI] [PubMed] [Google Scholar]
  20. Miller J., McLachlan A. D., Klug A. Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J. 1985 Jun;4(6):1609–1614. doi: 10.1002/j.1460-2075.1985.tb03825.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nietfeld W., el-Baradi T., Mentzel H., Pieler T., Köster M., Pöting A., Knöchel W. Second-order repeats in Xenopus laevis finger proteins. J Mol Biol. 1989 Aug 20;208(4):639–659. doi: 10.1016/0022-2836(89)90155-1. [DOI] [PubMed] [Google Scholar]
  22. Olson M., Hood L., Cantor C., Botstein D. A common language for physical mapping of the human genome. Science. 1989 Sep 29;245(4925):1434–1435. doi: 10.1126/science.2781285. [DOI] [PubMed] [Google Scholar]
  23. Pannuti A., Lanfrancone L., Pascucci A., Pelicci P. G., La Mantia G., Lania L. Isolation of cDNAs encoding finger proteins and measurement of the corresponding mRNA levels during myeloid terminal differentiation. Nucleic Acids Res. 1988 May 25;16(10):4227–4237. doi: 10.1093/nar/16.10.4227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pelham H. R., Brown D. D. A specific transcription factor that can bind either the 5S RNA gene or 5S RNA. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4170–4174. doi: 10.1073/pnas.77.7.4170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ruiz i Altaba A., Perry-O'Keefe H., Melton D. A. Xfin: an embryonic gene encoding a multifingered protein in Xenopus. EMBO J. 1987 Oct;6(10):3065–3070. doi: 10.1002/j.1460-2075.1987.tb02613.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ruppert J. M., Kinzler K. W., Wong A. J., Bigner S. H., Kao F. T., Law M. L., Seuanez H. N., O'Brien S. J., Vogelstein B. The GLI-Kruppel family of human genes. Mol Cell Biol. 1988 Aug;8(8):3104–3113. doi: 10.1128/mcb.8.8.3104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schuh R., Aicher W., Gaul U., Côté S., Preiss A., Maier D., Seifert E., Nauber U., Schröder C., Kemler R. A conserved family of nuclear proteins containing structural elements of the finger protein encoded by Krüppel, a Drosophila segmentation gene. Cell. 1986 Dec 26;47(6):1025–1032. doi: 10.1016/0092-8674(86)90817-2. [DOI] [PubMed] [Google Scholar]
  29. Thiesen H. J. Multiple genes encoding zinc finger domains are expressed in human T cells. New Biol. 1990 Apr;2(4):363–374. [PubMed] [Google Scholar]

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