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. 1994 Dec 1;13(23):5656–5667. doi: 10.1002/j.1460-2075.1994.tb06904.x

MAZ-dependent termination between closely spaced human complement genes.

R Ashfield 1, A J Patel 1, S A Bossone 1, H Brown 1, R D Campbell 1, K B Marcu 1, N J Proudfoot 1
PMCID: PMC395531  PMID: 7988563

Abstract

The zinc finger protein MAZ, originally identified as a factor that binds to the c-myc P2 promoter, is associated with transcriptional termination. As shown in these studies, a termination sequence between the closely spaced human complement genes C2 and Factor B contains a protein binding site which interacts with three different proteins in vitro. Binding of one of these factors, MAZ, correlates with activity of the C2 termination sequence in vivo. Cloned MAZ was used to obtain a consensus binding site, G5AG5. This allowed identification of new sites, between the closely spaced human genes g11 and C4 and within an intron of the mouse IgM-D gene, where termination is known to occur and regulate the expression of IgD. The g11 and IgM MAZ sites lie within sequences that have activity in a termination assay and, furthermore, mutation of C2 or g11 MAZ sites severely reduces termination activity. MAZ bends DNA, and inherently bent DNA is highly active as a terminator, suggesting that MAZ-induced bending is important for C2 and g11 termination. We propose that MAZ sites exist in promoters which require protection against transcriptional interference, such as those of closely spaced genes, to cause efficient termination. The MAZ consensus sequence will facilitate the identification of further sites.

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Selected References

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

  1. Ashfield R., Enriquez-Harris P., Proudfoot N. J. Transcriptional termination between the closely linked human complement genes C2 and factor B: common termination factor for C2 and c-myc? EMBO J. 1991 Dec;10(13):4197–4207. doi: 10.1002/j.1460-2075.1991.tb04998.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bartsch I., Schoneberg C., Grummt I. Purification and characterization of TTFI, a factor that mediates termination of mouse ribosomal DNA transcription. Mol Cell Biol. 1988 Sep;8(9):3891–3897. doi: 10.1128/mcb.8.9.3891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birnstiel M. L., Busslinger M., Strub K. Transcription termination and 3' processing: the end is in site! Cell. 1985 Jun;41(2):349–359. doi: 10.1016/s0092-8674(85)80007-6. [DOI] [PubMed] [Google Scholar]
  4. Björklund S., Skogman E., Thelander L. An S-phase specific release from a transcriptional block regulates the expression of mouse ribonucleotide reductase R2 subunit. EMBO J. 1992 Dec;11(13):4953–4959. doi: 10.1002/j.1460-2075.1992.tb05602.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blackwell T. K., Weintraub H. Differences and similarities in DNA-binding preferences of MyoD and E2A protein complexes revealed by binding site selection. Science. 1990 Nov 23;250(4984):1104–1110. doi: 10.1126/science.2174572. [DOI] [PubMed] [Google Scholar]
  6. Bossone S. A., Asselin C., Patel A. J., Marcu K. B. MAZ, a zinc finger protein, binds to c-MYC and C2 gene sequences regulating transcriptional initiation and termination. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7452–7456. doi: 10.1073/pnas.89.16.7452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chodchoy N., Pandey N. B., Marzluff W. F. An intact histone 3'-processing site is required for transcription termination in a mouse histone H2a gene. Mol Cell Biol. 1991 Jan;11(1):497–509. doi: 10.1128/mcb.11.1.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Connelly S., Manley J. L. A CCAAT box sequence in the adenovirus major late promoter functions as part of an RNA polymerase II termination signal. Cell. 1989 May 19;57(4):561–571. doi: 10.1016/0092-8674(89)90126-8. [DOI] [PubMed] [Google Scholar]
  9. Connelly S., Manley J. L. A functional mRNA polyadenylation signal is required for transcription termination by RNA polymerase II. Genes Dev. 1988 Apr;2(4):440–452. doi: 10.1101/gad.2.4.440. [DOI] [PubMed] [Google Scholar]
  10. Connelly S., Manley J. L. RNA polymerase II transcription termination is mediated specifically by protein binding to a CCAAT box sequence. Mol Cell Biol. 1989 Nov;9(11):5254–5259. doi: 10.1128/mcb.9.11.5254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Corbin V., Maniatis T. Role of transcriptional interference in the Drosophila melanogaster Adh promoter switch. Nature. 1989 Jan 19;337(6204):279–282. doi: 10.1038/337279a0. [DOI] [PubMed] [Google Scholar]
  12. Cullen B. R., Lomedico P. T., Ju G. Transcriptional interference in avian retroviruses--implications for the promoter insertion model of leukaemogenesis. Nature. 1984 Jan 19;307(5948):241–245. doi: 10.1038/307241a0. [DOI] [PubMed] [Google Scholar]
  13. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Edwalds-Gilbert G., Prescott J., Falck-Pedersen E. 3' RNA processing efficiency plays a primary role in generating termination-competent RNA polymerase II elongation complexes. Mol Cell Biol. 1993 Jun;13(6):3472–3480. doi: 10.1128/mcb.13.6.3472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Eggermont J., Proudfoot N. J. Poly(A) signals and transcriptional pause sites combine to prevent interference between RNA polymerase II promoters. EMBO J. 1993 Jun;12(6):2539–2548. doi: 10.1002/j.1460-2075.1993.tb05909.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Griffith J., Bleyman M., Rauch C. A., Kitchin P. A., Englund P. T. Visualization of the bent helix in kinetoplast DNA by electron microscopy. Cell. 1986 Aug 29;46(5):717–724. doi: 10.1016/0092-8674(86)90347-8. [DOI] [PubMed] [Google Scholar]
  18. Grosveld G. C., de Boer E., Shewmaker C. K., Flavell R. A. DNA sequences necessary for transcription of the rabbit beta-globin gene in vivo. Nature. 1982 Jan 14;295(5845):120–126. doi: 10.1038/295120a0. [DOI] [PubMed] [Google Scholar]
  19. Grummt I., Kuhn A., Bartsch I., Rosenbauer H. A transcription terminator located upstream of the mouse rDNA initiation site affects rRNA synthesis. Cell. 1986 Dec 26;47(6):901–911. doi: 10.1016/0092-8674(86)90805-6. [DOI] [PubMed] [Google Scholar]
  20. Hsieh C. H., Griffith J. D. The terminus of SV40 DNA replication and transcription contains a sharp sequence-directed curve. Cell. 1988 Feb 26;52(4):535–544. doi: 10.1016/0092-8674(88)90466-7. [DOI] [PubMed] [Google Scholar]
  21. Johnson M. R., Norman C., Reeve M. A., Scully J., Proudfoot N. J. Tripartite sequences within and 3' to the sea urchin H2A histone gene display properties associated with a transcriptional termination process. Mol Cell Biol. 1986 Nov;6(11):4008–4018. doi: 10.1128/mcb.6.11.4008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jones K. A., Kadonaga J. T., Luciw P. A., Tjian R. Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. Science. 1986 May 9;232(4751):755–759. doi: 10.1126/science.3008338. [DOI] [PubMed] [Google Scholar]
  23. Kerppola T. K., Kane C. M. Analysis of the signals for transcription termination by purified RNA polymerase II. Biochemistry. 1990 Jan 9;29(1):269–278. doi: 10.1021/bi00453a037. [DOI] [PubMed] [Google Scholar]
  24. Kim J., Zwieb C., Wu C., Adhya S. Bending of DNA by gene-regulatory proteins: construction and use of a DNA bending vector. Gene. 1989 Dec 21;85(1):15–23. doi: 10.1016/0378-1119(89)90459-9. [DOI] [PubMed] [Google Scholar]
  25. Kitchin P. A., Klein V. A., Ryan K. A., Gann K. L., Rauch C. A., Kang D. S., Wells R. D., Englund P. T. A highly bent fragment of Crithidia fasciculata kinetoplast DNA. J Biol Chem. 1986 Aug 25;261(24):11302–11309. [PubMed] [Google Scholar]
  26. Kuhn A., Bartsch I., Grummt I. Specific interaction of the murine transcription termination factor TTF I with class-I RNA polymerases. Nature. 1990 Apr 5;344(6266):559–562. doi: 10.1038/344559a0. [DOI] [PubMed] [Google Scholar]
  27. Kunkel G. R., Pederson T. Transcription boundaries of U1 small nuclear RNA. Mol Cell Biol. 1985 Sep;5(9):2332–2340. doi: 10.1128/mcb.5.9.2332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kuziel W. A., Word C. J., Yuan D., White M. B., Mushinski J. F., Blattner F. R., Tucker P. W. The human immunoglobulin C mu-C delta locus: regulation of mu and delta RNA expression during B cell development. Int Immunol. 1989;1(3):310–319. doi: 10.1093/intimm/1.3.310. [DOI] [PubMed] [Google Scholar]
  29. Lanoix J., Acheson N. H. A rabbit beta-globin polyadenylation signal directs efficient termination of transcription of polyomavirus DNA. EMBO J. 1988 Aug;7(8):2515–2522. doi: 10.1002/j.1460-2075.1988.tb03099.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lanzer M., de Bruin D., Ravetch J. V. Transcription mapping of a 100 kb locus of Plasmodium falciparum identifies an intergenic region in which transcription terminates and reinitiates. EMBO J. 1992 May;11(5):1949–1955. doi: 10.1002/j.1460-2075.1992.tb05248.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Levitt N., Briggs D., Gil A., Proudfoot N. J. Definition of an efficient synthetic poly(A) site. Genes Dev. 1989 Jul;3(7):1019–1025. doi: 10.1101/gad.3.7.1019. [DOI] [PubMed] [Google Scholar]
  32. Logan J., Falck-Pedersen E., Darnell J. E., Jr, Shenk T. A poly(A) addition site and a downstream termination region are required for efficient cessation of transcription by RNA polymerase II in the mouse beta maj-globin gene. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8306–8310. doi: 10.1073/pnas.84.23.8306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mather E. L., Nelson K. J., Haimovich J., Perry R. P. Mode of regulation of immunoglobulin mu- and delta-chain expression varies during B-lymphocyte maturation. Cell. 1984 Feb;36(2):329–338. doi: 10.1016/0092-8674(84)90226-5. [DOI] [PubMed] [Google Scholar]
  34. Miller H., Asselin C., Dufort D., Yang J. Q., Gupta K., Marcu K. B., Nepveu A. A cis-acting element in the promoter region of the murine c-myc gene is necessary for transcriptional block. Mol Cell Biol. 1989 Dec;9(12):5340–5349. doi: 10.1128/mcb.9.12.5340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Pribyl T. M., Martinson H. G. Transcription termination at the chicken beta H-globin gene. Mol Cell Biol. 1988 Dec;8(12):5369–5377. doi: 10.1128/mcb.8.12.5369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Proudfoot N. J. Transcriptional interference and termination between duplicated alpha-globin gene constructs suggests a novel mechanism for gene regulation. Nature. 1986 Aug 7;322(6079):562–565. doi: 10.1038/322562a0. [DOI] [PubMed] [Google Scholar]
  37. Pyrc J. J., Moberg K. H., Hall D. J. Isolation of a novel cDNA encoding a zinc-finger protein that binds to two sites within the c-myc promoter. Biochemistry. 1992 Apr 28;31(16):4102–4110. doi: 10.1021/bi00131a029. [DOI] [PubMed] [Google Scholar]
  38. Renucci A., Zappavigna V., Zàkàny J., Izpisúa-Belmonte J. C., Bürki K., Duboule D. Comparison of mouse and human HOX-4 complexes defines conserved sequences involved in the regulation of Hox-4.4. EMBO J. 1992 Apr;11(4):1459–1468. doi: 10.1002/j.1460-2075.1992.tb05190.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Roberts S., Purton T., Bentley D. L. A protein-binding site in the c-myc promoter functions as a terminator of RNA polymerase II transcription. Genes Dev. 1992 Aug;6(8):1562–1574. doi: 10.1101/gad.6.8.1562. [DOI] [PubMed] [Google Scholar]
  40. Skarnes W. C., Tessier D. C., Acheson N. H. RNA polymerases stall and/or prematurely terminate nearby both early and late promoters on polyomavirus DNA. J Mol Biol. 1988 Sep 5;203(1):153–171. doi: 10.1016/0022-2836(88)90099-x. [DOI] [PubMed] [Google Scholar]
  41. Thompson J. F., Landy A. Empirical estimation of protein-induced DNA bending angles: applications to lambda site-specific recombination complexes. Nucleic Acids Res. 1988 Oct 25;16(20):9687–9705. doi: 10.1093/nar/16.20.9687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Vales L. D., Darnell J. E., Jr Promoter occlusion prevents transcription of adenovirus polypeptide IX mRNA until after DNA replication. Genes Dev. 1989 Jan;3(1):49–59. doi: 10.1101/gad.3.1.49. [DOI] [PubMed] [Google Scholar]
  43. Weichs an der Glon C., Monks J., Proudfoot N. J. Occlusion of the HIV poly(A) site. Genes Dev. 1991 Feb;5(2):244–253. doi: 10.1101/gad.5.2.244. [DOI] [PubMed] [Google Scholar]
  44. Whitelaw E., Proudfoot N. Alpha-thalassaemia caused by a poly(A) site mutation reveals that transcriptional termination is linked to 3' end processing in the human alpha 2 globin gene. EMBO J. 1986 Nov;5(11):2915–2922. doi: 10.1002/j.1460-2075.1986.tb04587.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wright S., Mirels L. F., Calayag M. C., Bishop J. M. Premature termination of transcription from the P1 promoter of the mouse c-myc gene. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11383–11387. doi: 10.1073/pnas.88.24.11383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wu H. M., Crothers D. M. The locus of sequence-directed and protein-induced DNA bending. Nature. 1984 Apr 5;308(5959):509–513. doi: 10.1038/308509a0. [DOI] [PubMed] [Google Scholar]
  47. Wu L. C., Morley B. J., Campbell R. D. Cell-specific expression of the human complement protein factor B gene: evidence for the role of two distinct 5'-flanking elements. Cell. 1987 Jan 30;48(2):331–342. doi: 10.1016/0092-8674(87)90436-3. [DOI] [PubMed] [Google Scholar]
  48. Yuan D., Tucker P. W. Transcriptional regulation of the mu-delta heavy chain locus in normal murine B lymphocytes. J Exp Med. 1984 Aug 1;160(2):564–583. doi: 10.1084/jem.160.2.564. [DOI] [PMC free article] [PubMed] [Google Scholar]

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