DOI: 10.1126/science.282.5396.2018. Zinc Fingers in <i>Caenorhabditis elegans</i> : Finding Families and Probing Pathways

Zinc Fingers in Caenorhabditis elegans : Finding Families and Probing Pathways

10.1126/science.282.5396.2018

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

More than 3 percent of the protein sequences inferred from the Caenorhabditis elegans genome contain sequence motifs characteristic of zinc-binding structural domains, and of these more than half are believed to be sequence-specific DNA-binding proteins. The distribution of these zinc-binding domains among the genomes of various organisms offers insights into the role of zinc-binding proteins in evolution. In addition, the complete genome sequence of C. elegans provides an opportunity to analyze, and perhaps predict, pathways of transcriptional regulation.

Bibliography

Clarke, N. D., & Berg, J. M. (1998). Zinc Fingers in Caenorhabditis elegans â¯: Finding Families and Probing Pathways. Science, 282(5396), 2018â2022.

Authors 2

Neil D. Clarke (first)
Jeremy M. Berg (additional)

References 40 Referenced 154

10.1002/j.1460-2075.1985.tb03825.x
10.1016/0014-5793(85)80723-7
Böhm S., Drescher B., Stud. Biophys. 107, 237 (1985). / Stud. Biophys. by Böhm S. (1985)
10.1126/science.271.5252.1081
10.1073/pnas.85.1.99
10.1126/science.3047872
Lee M. S., Gippert G. P., Soman K. V., Case D. A., Wright P. E., ibid. 245, 635 (1989). / ibid. by Lee M. S. (1989)
10.1093/nar/25.12.2464
10.1038/nsb0694-388
J. W. Schwabe and A. Klug ibid. p. 345.
10.1002/j.1460-2075.1992.tb05139.x
10.1093/nar/21.16.3691
10.1016/0092-8674(92)90099-X
10.1126/science.8378770
10.1093/genetics/86.2.275
10.1101/gad.1.7.731
10.1038/344721a0
10.1093/genetics/123.4.755
10.1016/0092-8674(88)90117-1
10.1038/35618
10.1016/S0959-440X(96)80056-X
Data from (12) were used to generate in the computer a large number of sequences having the same overall distribution of nucleotide preferences as those determined experimentally for selected tra-1 –binding sites. The sequences were then used to construct an HMM with the “hmmbuild-f” program in HMMER v2.0 (hmmer.wustl.edu). In the same way an HMM for the complementary site was constructed with sequences complementary to those used to construct the first HMM. This allows searches to be conducted for both orientations of the site. Because the amount of information in short DNA sequences is low relative to the size of the genome the significance of even a good match to the HMM is considered suspect by the “hmmsearch” program and only the first hit in the entire genome is output. To allow all matches in the genome to be detected we artificially increased the significance of a match by doubling the match state scores in the HMMs. With these modified HMMs a score threshold of 15 correlated subjectively well with similarity to the consensus TRA-1A site and was used for all further analyses of TRA-1A sites. With this criterion 1299 sites were found in the C. elegans genome. These and other search results can be found at www.sciencemag.org/feature/data/985286.shl. The same procedure was used to identify potential MAB-3 sites with unpublished binding site selection experiments (25). At a score threshold of 20 1346 sites were identified in the C. elegans genome. A similar strategy was also used to identify ELT-1–binding sites except in this case a score cutoff was chosen that allowed only perfect matches to the consensus sequence (A/T)GATA(A/G). Over 200 000 sites were found.
10.1101/gad.7.6.933
C03C11.2 has five upstream tra-1 sites and is homologous to a protein called Tob (transducer of erbB-2) (36). F08F3.9 has three upstream sites and is homologous to SNAP45 a human TAF (37).
D. Zarkower personal communication.
10.1038/341335a0
D. Stanojevic T. Hoey M. Levine ibid. p. 331.
10.1093/genetics/144.4.1639
N. D. Clarke and J. M. Berg data not shown.
Spieth J., Shim Y. H., Lea K., Conrad R., Blumenthal T., Mol. Cell. Biol. 11, 4651 (1991). / Mol. Cell. Biol. by Spieth J. (1991)
10.1126/science.282.5389.699
10.1073/pnas.89.16.7345
10.1021/bi981358z
10.1146/annurev.nutr.18.1.441
10.1152/physrev.1993.73.1.79
Matsuda S., et al., Oncogene 12, 705 (1996). / Oncogene by Matsuda S. (1996)
10.1038/374653a0
10.1002/(SICI)1097-0134(199707)28:3<405::AID-PROT10>3.0.CO;2-L
10.1073/pnas.93.24.13754
We thank all involved in the sequencing of the C. elegans genome for providing the raw material for this analysis. We especially thank L. Hillier and J. Spieth at the Washington University Genome Sequencing Center for their help in running preliminary searches providing data files and promptly answering all of our technical questions. We are also grateful to D. Zarkower for helpful comments on the manuscript to W. Yi and D. Zarkower for sharing MAB-3 binding data before publication and to J. Hodgkin for alerting us to the existence of these data. Research on zinc-binding proteins in the laboratory of J.M.B. has been supported by NIH and Sangamo Biosciences. J.M.B. is a member of the Scientific Advisory Board of Sangamo Biosciences. N.D.C. received salary support from the National Institute of Standards and Technology while on a part-time sabbatical.

Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 5:37 a.m.)
Deposited	1 year, 7 months ago (Jan. 13, 2024, 12:29 a.m.)
Indexed	1 month ago (Aug. 5, 2025, 8:55 a.m.)
Issued	26 years, 8 months ago (Dec. 11, 1998)
Published	26 years, 8 months ago (Dec. 11, 1998)
Published Print	26 years, 8 months ago (Dec. 11, 1998)

Funders 0

None

BibTeX

@article{Clarke_1998, title={Zinc Fingers in Caenorhabditis elegans  : Finding Families and Probing Pathways}, volume={282}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.282.5396.2018}, DOI={10.1126/science.282.5396.2018}, number={5396}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Clarke, Neil D. and Berg, Jeremy M.}, year={1998}, month=dec, pages={2018–2022} }

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