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. 1991 Nov 1;88(21):9799–9803. doi: 10.1073/pnas.88.21.9799

Delta, a transcription factor that binds to downstream elements in several polymerase II promoters, is a functionally versatile zinc finger protein.

N Hariharan 1, D E Kelley 1, R P Perry 1
PMCID: PMC52808  PMID: 1946404

Abstract

The promoters of several eukaryotic genes transcribed by RNA polymerase II contain elements located downstream of the transcriptional start site. To gain insight into how these elements function in the formation of an active transcription complex, we have cloned and sequenced the cDNA that encodes delta, a protein that binds to critical downstream promoter elements in the mouse ribosomal protein rpL30 and rpL32 genes. Our results revealed that the delta protein contains four C-terminal zinc fingers, which are essential for its DNA binding capability and a very unusual N-terminal domain that includes stretches of 11 consecutive negatively charged amino acids and 12 consecutive histidines. The sequence of the delta protein was found to be essentially identical to a concurrently cloned human transcription factor that acts both positively and negatively in the context of immunoglobulin enhancers and a viral promoter. Our structural modeling of this protein indicates properties that could endow it with exquisite functional versatility.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atchison M. L., Meyuhas O., Perry R. P. Localization of transcriptional regulatory elements and nuclear factor binding sites in mouse ribosomal protein gene rpL32. Mol Cell Biol. 1989 May;9(5):2067–2074. doi: 10.1128/mcb.9.5.2067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ayer D. E., Dynan W. S. A downstream-element-binding factor facilitates assembly of a functional preinitiation complex at the simian virus 40 major late promoter. Mol Cell Biol. 1990 Jul;10(7):3635–3645. doi: 10.1128/mcb.10.7.3635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beckmann H., Su L. K., Kadesch T. TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer muE3 motif. Genes Dev. 1990 Feb;4(2):167–179. doi: 10.1101/gad.4.2.167. [DOI] [PubMed] [Google Scholar]
  4. Cohen R. B., Yang L., Thompson J. A., Safer B. Identification of a downstream sequence and binding protein that regulate adenovirus major late promoter transcription in vitro. J Biol Chem. 1988 Jul 25;263(21):10377–10385. [PubMed] [Google Scholar]
  5. Farnham P. J., Means A. L. Sequences downstream of the transcription initiation site modulate the activity of the murine dihydrofolate reductase promoter. Mol Cell Biol. 1990 Apr;10(4):1390–1398. doi: 10.1128/mcb.10.4.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  7. Hariharan N., Kelley D. E., Perry R. P. Equipotent mouse ribosomal protein promoters have a similar architecture that includes internal sequence elements. Genes Dev. 1989 Nov;3(11):1789–1800. doi: 10.1101/gad.3.11.1789. [DOI] [PubMed] [Google Scholar]
  8. Hariharan N., Perry R. P. A characterization of the elements comprising the promoter of the mouse ribosomal protein gene RPS16. Nucleic Acids Res. 1989 Jul 11;17(13):5323–5337. doi: 10.1093/nar/17.13.5323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hosler B. A., LaRosa G. J., Grippo J. F., Gudas L. J. Expression of REX-1, a gene containing zinc finger motifs, is rapidly reduced by retinoic acid in F9 teratocarcinoma cells. Mol Cell Biol. 1989 Dec;9(12):5623–5629. doi: 10.1128/mcb.9.12.5623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kelley D. E., Pollok B. A., Atchison M. L., Perry R. P. The coupling between enhancer activity and hypomethylation of kappa immunoglobulin genes is developmentally regulated. Mol Cell Biol. 1988 Feb;8(2):930–937. doi: 10.1128/mcb.8.2.930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kozak M. The scanning model for translation: an update. J Cell Biol. 1989 Feb;108(2):229–241. doi: 10.1083/jcb.108.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  13. Lennard A. C., Fried M. The bidirectional promoter of the divergently transcribed mouse Surf-1 and Surf-2 genes. Mol Cell Biol. 1991 Mar;11(3):1281–1294. doi: 10.1128/mcb.11.3.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Meyuhas O., Klein A. The mouse ribosomal protein L7 gene. Its primary structure and functional analysis of the promoter region. J Biol Chem. 1990 Jul 15;265(20):11465–11473. [PubMed] [Google Scholar]
  15. Mitchell M. T., Benfield P. A. Two different RNA polymerase II initiation complexes can assemble on the rat brain creatine kinase promoter. J Biol Chem. 1990 May 15;265(14):8259–8267. [PubMed] [Google Scholar]
  16. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  17. Moura-Neto R., Dudov K. P., Perry R. P. An element downstream of the cap site is required for transcription of the gene encoding mouse ribosomal protein L32. Proc Natl Acad Sci U S A. 1989 Jun;86(11):3997–4001. doi: 10.1073/pnas.86.11.3997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Park K., Atchison M. L. Isolation of a candidate repressor/activator, NF-E1 (YY-1, delta), that binds to the immunoglobulin kappa 3' enhancer and the immunoglobulin heavy-chain mu E1 site. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9804–9808. doi: 10.1073/pnas.88.21.9804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pavletich N. P., Pabo C. O. Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science. 1991 May 10;252(5007):809–817. doi: 10.1126/science.2028256. [DOI] [PubMed] [Google Scholar]
  20. Ptashne M., Gann A. A. Activators and targets. Nature. 1990 Jul 26;346(6282):329–331. doi: 10.1038/346329a0. [DOI] [PubMed] [Google Scholar]
  21. Riggs K. J., Merrell K. T., Wilson G., Calame K. Common factor 1 is a transcriptional activator which binds in the c-myc promoter, the skeletal alpha-actin promoter, and the immunoglobulin heavy-chain enhancer. Mol Cell Biol. 1991 Mar;11(3):1765–1769. doi: 10.1128/mcb.11.3.1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ross A. M., Golub E. E. A computer graphics program system for protein structure representation. Nucleic Acids Res. 1988 Mar 11;16(5):1801–1812. doi: 10.1093/nar/16.5.1801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sharp P. A. Gene transcription. TFIIB or not TFIIB? Nature. 1991 May 2;351(6321):16–18. doi: 10.1038/351016d0. [DOI] [PubMed] [Google Scholar]
  24. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  25. Shi Y., Seto E., Chang L. S., Shenk T. Transcriptional repression by YY1, a human GLI-Krüppel-related protein, and relief of repression by adenovirus E1A protein. Cell. 1991 Oct 18;67(2):377–388. doi: 10.1016/0092-8674(91)90189-6. [DOI] [PubMed] [Google Scholar]
  26. Singh H., LeBowitz J. H., Baldwin A. S., Jr, Sharp P. A. Molecular cloning of an enhancer binding protein: isolation by screening of an expression library with a recognition site DNA. Cell. 1988 Feb 12;52(3):415–423. doi: 10.1016/s0092-8674(88)80034-5. [DOI] [PubMed] [Google Scholar]
  27. Vinson C. R., LaMarco K. L., Johnson P. F., Landschulz W. H., McKnight S. L. In situ detection of sequence-specific DNA binding activity specified by a recombinant bacteriophage. Genes Dev. 1988 Jul;2(7):801–806. doi: 10.1101/gad.2.7.801. [DOI] [PubMed] [Google Scholar]
  28. Wickens M. In the beginning is the end: regulation of poly(A) addition and removal during early development. Trends Biochem Sci. 1990 Aug;15(8):320–324. doi: 10.1016/0968-0004(90)90022-4. [DOI] [PubMed] [Google Scholar]
  29. Yang J. Q., Remmers E. F., Marcu K. B. The first exon of the c-myc proto-oncogene contains a novel positive control element. EMBO J. 1986 Dec 20;5(13):3553–3562. doi: 10.1002/j.1460-2075.1986.tb04682.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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