Skip to main content
Log in

Structure and Basal Transcription Complex of RNA Polymerase II Core Promoters in the Mammalian Genome: An Overview

  • Review
  • Published:
Molecular Biotechnology Aims and scope Submit manuscript

Abstract

The mammalian core promoter is a sophisticated and crucial component for the regulation of transcription mediated by the RNA polymerase II. It is generally defined as the minimal region of contiguous DNA sequence that is sufficient to accurately initiate a basal level of gene expression. The core promoter represents the ultimate target for nucleation of a functional pre-initiation complex composed of the RNA polymerase II and associated general transcription factors. Among the more than 40 distinct proteins assembling the basal transcription complex, TFIID plays a central role in recognizing and binding specific core promoter elements to support creating an environment that facilitates transcription initiation. Several common DNA motifs, like the TATA box, initiator region, or the downstream promoter element, are found in a subset of core promoters present in various combinations. Another class of promoters that is usually absent of a TATA box is constituted by the so-called CpG islands, which are associated with the majority of protein-coding genes within the mammalian genome.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Butler, J., & Kadonaga, J. (2002). The RNA polymerase II core promoter: A key component in the regulation of gene expression. Genes and Development, 16, 2583–2592.

    Article  CAS  Google Scholar 

  2. Smale, S., & Baltimore, D. (1989). The “initiator” as a transcription control element. Cell, 57, 103–113.

    Article  CAS  Google Scholar 

  3. Smale, S. (1997). Transcription initiation from TATA-less promoters within eukaryotic protein-coding genes. Biochimica et Biophysica Acta, 1351, 73–88.

    CAS  Google Scholar 

  4. Smale, S. (2001). Core promoters: Active contributors to combinatorial gene regulation. Genes and Development, 15, 2503–2508.

    Article  CAS  Google Scholar 

  5. Blackwood, E., & Kadonaga, J. (1998). Going the distance: A current view of enhancer action. Science, 281, 60–63.

    Article  CAS  Google Scholar 

  6. Bulger, M., & Groudine, M. (1999). Looping versus linking: Toward a model for long-distance gene activation. Genes and Development, 13, 2465–2477.

    Article  CAS  Google Scholar 

  7. West, A., Gaszner, M., & Felsenfeld, G. (2002). Insulators: Many functions, many mechanisms. Genes and Development, 16, 271–288.

    Article  CAS  Google Scholar 

  8. Burley, S., & Roeder, R. (1996). Biochemistry and structural biology of transcription factor IID (TFIID). Annual Review of Biochemistry, 65, 769–799.

    Article  CAS  Google Scholar 

  9. Orphanides, G., Lagrange, T., & Reinberg, D. (1996). The general transcription factors of RNA polymerase II. Genes and Development, 10, 2657–2683.

    Article  CAS  Google Scholar 

  10. Hampsey, M. (1998). Molecular genetics of the RNA polymerase II general transcriptional machinery. Microbiology and Molecular Biology Reviews, 62, 465–503.

    CAS  Google Scholar 

  11. Roeder, R. (1998). Role of general and gene-specific cofactors in the regulation of eukaryotic transcription. Cold Spring Harbor Symposia on Quantitative Biology, 63, 201–218.

    Article  CAS  Google Scholar 

  12. Lemon, B., & Tjian, R. (2000). Orchestrated response: A symphony of transcription factors for gene control. Genes and Development, 14, 2551–2569.

    Article  CAS  Google Scholar 

  13. Strahl, B., & Allis, C. (2000). The language of covalent histone modifications. Nature, 403, 41–45.

    Article  CAS  Google Scholar 

  14. Courey, A., & Jia, S. (2001). Transcriptional repression: The long and the short of it. Genes and Development, 15, 2786–2796.

    CAS  Google Scholar 

  15. Zhang, Y., & Reinberg, D. (2001). Transcription regulation by histone methylation: Interplay between different covalent modifications of the core histone tails. Genes and Development, 15, 2343–2360.

    Article  CAS  Google Scholar 

  16. Narlikar, G., Fan, H., & Kingston, R. (2002). Cooperation between complexes that regulate chromatin structure and transcription. Cell, 108, 475–487.

    Article  CAS  Google Scholar 

  17. Orphanides, G., & Reinberg, D. (2002). A unified theory of gene expression. Cell, 108, 439–451.

    Article  CAS  Google Scholar 

  18. Spenger, A., Ernst, W., Condreay, J., Kost, T., & Grabherr, R. (2004). Influence of promoter choice and trichostatin. A treatment on expression of baculovirus delivered genes in mammalian cells. Protein Expression and Purification, 38, 17–23.

    Article  CAS  Google Scholar 

  19. Goldberg. M. L. (1979). PhD thesis, Stanford University, California.

  20. Breathnach, R., & Chambon, P. (1981). Organization and expression of eucaryotic split genes coding for proteins. Annual Review of Biochemistry, 50, 349–383.

    Article  CAS  Google Scholar 

  21. Carninci, P., Sandelin, A., Lenhard, B., Katayama, S., Shimokawa, K., Ponjavic, J., et al. (2006). Genome-wide analysis of mammalian promoter architecture and evolution. Nature Genetics, 38, 626–635.

    Article  CAS  Google Scholar 

  22. Suzuki, Y., Tsunoda, T., Sese, J., Taira, H., Mizushima-Sugano, J., Hata, H., et al. (2001). Identification and characterization of the potential promoter regions of 1031 kinds of human genes. Genome Research, 11, 677–684.

    Article  CAS  Google Scholar 

  23. Smale, S., & Kadonaga, J. (2003). The RNA polymerase II core promoter. Annual Review of Biochemistry, 72, 449–479.

    Article  CAS  Google Scholar 

  24. Corden, J., Wasylyk, B., Buchwalder, A., Sassone-Corsi, P., Kedinger, C., & Chambon, P. (1980). Promoter sequences of eukaryotic protein-coding genes. Science, 209, 1406–1414.

    Article  CAS  Google Scholar 

  25. Struhl, K. (1987). Promoters, activator proteins, and the mechanism of transcriptional initiation in yeast. Cell, 49, 295–297.

    Article  CAS  Google Scholar 

  26. Bucher, P. (1990). Weight matrix descriptions of four eukaryotic RNA polymerase II promoter elements derived from 502 unrelated promoter sequences. Journal of Molecular Biology, 212, 563–578.

    Article  CAS  Google Scholar 

  27. Javahery, R., Khachi, A., Lo, K., Zenzie-Gregory, B., & Smale, S. (1994). DNA sequence requirements for transcriptional initiator activity in mammalian cells. Molecular and Cellular Biology, 14, 116–127.

    CAS  Google Scholar 

  28. Lo, K., & Smale, S. (1996). Generality of a functional initiator consensus sequence. Gene, 182, 13–22.

    Article  CAS  Google Scholar 

  29. Smale, S., Jain, A., Kaufmann, J., Emami, K., Lo, K., & Garraway, I. (1998). The initiator element: A paradigm for core promoter heterogeneity within metazoan protein-coding genes. Cold Spring Harbor Symposia on Quantitative Biology, 63, 21–31.

    Article  CAS  Google Scholar 

  30. Zhou, T., & Chiang, C. (2001). The intronless and TATA-less human TAF(II)55 gene contains a functional initiator and a downstream promoter element. The Journal of Biological Chemistry, 276, 25503–25511.

    Article  CAS  Google Scholar 

  31. Chalkley, G., & Verrijzer, C. (1999). DNA binding site selection by RNA polymerase II TAFs: A TAF(II)250-TAF(II)150 complex recognizes the initiator. EMBO Journal, 18, 4835–4845.

    Article  CAS  Google Scholar 

  32. Burke, T., & Kadonaga, J. (1997). The downstream core promoter element, DPE, is conserved from Drosophila to humans and is recognized by TAFII60 of Drosophila. Genes and Development, 11, 3020–3031.

    Article  CAS  Google Scholar 

  33. Burke, T., & Kadonaga, J. (1996). Drosophila TFIID binds to a conserved downstream basal promoter element that is present in many TATA-box-deficient promoters. Genes and Development, 10, 711–724.

    Article  CAS  Google Scholar 

  34. Kadonaga, J. (2002). The DPE, a core promoter element for transcription by RNA polymerase II. Experimental and Molecular Medicine, 34, 259–264.

    CAS  Google Scholar 

  35. Kutach, A., & Kadonaga, J. (2000). The downstream promoter element DPE appears to be as widely used as the TATA box in Drosophila core promoters. Molecular and Cellular Biology, 20, 4754–4764.

    Article  CAS  Google Scholar 

  36. Mizrokhi, L., Georgieva, S., & Il’in, I. (1988). Drosophila mobile element jockey is transcribed from the internal promoter by RNA-polymerase II. Dokl Akad Nauk SSSR, 301, 1250–1254.

    CAS  Google Scholar 

  37. Lagrange, T., Kapanidis, A., Tang, H., Reinberg, D., & Ebright, R. (1998). New core promoter element in RNA polymerase II-dependent transcription: Sequence-specific DNA binding by transcription factor IIB. Genes and Development, 12, 34–44.

    Article  CAS  Google Scholar 

  38. Deng, W., & Roberts, S. (2005). A core promoter element downstream of the TATA box that is recognized by TFIIB. Genes and Development, 19, 2418–2423.

    Article  CAS  Google Scholar 

  39. Deng, W., & Roberts, S. (2007). TFIIB and the regulation of transcription by RNA polymerase II. Chromosoma, 116, 417–429.

    Article  CAS  Google Scholar 

  40. Lewis, B., Kim, T., & Orkin, S. (2000). A downstream element in the human beta-globin promoter: Evidence of extended sequence-specific transcription factor IID contacts. Proceedings of the National Academy of Sciences of the United States of America, 97, 7172–7177.

    Article  CAS  Google Scholar 

  41. Lee, D., Gershenzon, N., Gupta, M., Ioshikhes, I., Reinberg, D., & Lewis, B. (2005). Functional characterization of core promoter elements: The downstream core element is recognized by TAF1. Molecular and Cellular Biology, 25, 9674–9686.

    Article  CAS  Google Scholar 

  42. Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes and Development, 16, 6–21.

    Article  CAS  Google Scholar 

  43. Monk, M., Boubelik, M., & Lehnert, S. (1987). Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development, 99, 371–382.

    CAS  Google Scholar 

  44. Kafri, T., Ariel, M., Brandeis, M., Shemer, R., Urven, L., McCarrey, J., et al. (1992). Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line. Genes and Development, 6, 705–714.

    Article  CAS  Google Scholar 

  45. Bird, A. (1986). CpG-rich islands and the function of DNA methylation. Nature, 321, 209–213.

    Article  CAS  Google Scholar 

  46. Gardiner-Garden, M., & Frommer, M. (1987). CpG islands in vertebrate genomes. Journal of Molecular Biology, 196, 261–282.

    Article  CAS  Google Scholar 

  47. Antequera, F., & Bird, A. (1993). Number of CpG islands and genes in human and mouse. Proceedings of the National Academy of Sciences of the United States of America, 90, 11995–11999.

    Article  CAS  Google Scholar 

  48. Larsen, F., Gundersen, G., Lopez, R., & Prydz, H. (1992). CpG islands as gene markers in the human genome. Genomics, 13, 1095–1107.

    Article  CAS  Google Scholar 

  49. Cross, S., & Bird, A. (1995). CpG islands and genes. Current Opinion in Genetics and Development, 5, 309–314.

    Article  CAS  Google Scholar 

  50. Boyes, J., & Bird, A. (1992). Repression of genes by DNA methylation depends on CpG density and promoter strength: Evidence for involvement of a methyl-CpG binding protein. EMBO Journal, 11, 327–333.

    CAS  Google Scholar 

  51. Brandeis, M., Frank, D., Keshet, I., Siegfried, Z., Mendelsohn, M., Nemes, A., et al. (1994). Sp1 elements protect a CpG island from de novo methylation. Nature, 371, 435–438.

    Article  CAS  Google Scholar 

  52. Macleod, D., Charlton, J., Mullins, J., & Bird, A. (1994). Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes and Development, 8, 2282–2292.

    Article  CAS  Google Scholar 

  53. Kim, T., Barrera, L., Zheng, M., Qu, C., Singer, M., Richmond, T., et al. (2005). A high-resolution map of active promoters in the human genome. Nature, 436, 876–880.

    Article  CAS  Google Scholar 

  54. Bajic, V., Tan, S., Christoffels, A., Schönbach, C., Lipovich, L., Yang, L., et al. (2006). Mice and men: Their promoter properties. PLoS Genetics, 2, e54.

    Article  CAS  Google Scholar 

  55. Bajic, V., Choudhary, V., & Hock, C. (2004). Content analysis of the core promoter region of human genes. In Silico Biology, 4, 109–125.

    CAS  Google Scholar 

  56. Cooper, S., Trinklein, N., Anton, E., Nguyen, L., & Myers, R. (2006). Comprehensive analysis of transcriptional promoter structure and function in 1% of the human genome. Genome Research, 16, 1–10.

    Article  CAS  Google Scholar 

  57. Roeder, R. (1996). The role of general initiation factors in transcription by RNA polymerase II. Trends in Biochemical Sciences, 21, 327–335.

    CAS  Google Scholar 

  58. Zawel, L., & Reinberg, D. (1993). Initiation of transcription by RNA polymerase II: A multi-step process. Progress in Nucleic Acid Research and Molecular Biology, 44, 67–108.

    Article  CAS  Google Scholar 

  59. Weil, P., Luse, D., Segall, J., & Roeder, R. (1979). Selective and accurate initiation of transcription at the Ad2 major late promotor in a soluble system dependent on purified RNA polymerase II and DNA. Cell, 18, 469–484.

    Article  CAS  Google Scholar 

  60. Matsui, T., Segall, J., Weil, P., & Roeder, R. (1980). Multiple factors required for accurate initiation of transcription by purified RNA polymerase II. The Journal of Biological Chemistry, 255, 11992–11996.

    CAS  Google Scholar 

  61. Samuels, M., Fire, A., & Sharp, P. (1982). Separation and characterization of factors mediating accurate transcription by RNA polymerase II. The Journal of Biological Chemistry, 257, 14419–14427.

    CAS  Google Scholar 

  62. Sawadogo, M., & Roeder, R. (1985). Interaction of a gene-specific transcription factor with the adenovirus major late promoter upstream of the TATA box region. Cell, 43, 165–175.

    Article  CAS  Google Scholar 

  63. Reinberg, D., & Roeder, R. (1987). Factors involved in specific transcription by mammalian RNA polymerase II. Purification and functional analysis of initiation factors IIB and IIE. The Journal of Biological Chemistry, 262, 3310–3321.

    CAS  Google Scholar 

  64. Flores, O., Maldonado, E., & Reinberg, D. (1989). Factors involved in specific transcription by mammalian RNA polymerase II. Factors IIE and IIF independently interact with RNA polymerase II. The Journal of Biological Chemistry, 264, 8913–8921.

    CAS  Google Scholar 

  65. Flores, O., Lu, H., & Reinberg, D. (1992). Factors involved in specific transcription by mammalian RNA polymerase II. Identification and characterization of factor IIH. The Journal of Biological Chemistry, 267, 2786–2793.

    CAS  Google Scholar 

  66. Ge, H., Martinez, E., Chiang, C., & Roeder, R. (1996). Activator-dependent transcription by mammalian RNA polymerase II: In vitro reconstitution with general transcription factors and cofactors. Methods in Enzymology, 274, 57–71.

    Article  CAS  Google Scholar 

  67. Buratowski, S., Hahn, S., Guarente, L., & Sharp, P. (1989). Five intermediate complexes in transcription initiation by RNA polymerase II. Cell, 56, 549–561.

    Article  CAS  Google Scholar 

  68. Malik, S., & Roeder, R. (2000). Transcriptional regulation through Mediator-like coactivators in yeast and metazoan cells. Trends in Biochemical Sciences, 25, 277–283.

    Article  CAS  Google Scholar 

  69. Ossipow, V., Tassan, J., Nigg, E., & Schibler, U. (1995). A mammalian RNA polymerase II holoenzyme containing all components required for promoter-specific transcription initiation. Cell, 83, 137–146.

    Article  CAS  Google Scholar 

  70. Chao, D., Gadbois, E., Murray, P., Anderson, S., Sonu, M., Parvin, J., et al. (1996). A mammalian SRB protein associated with an RNA polymerase II holoenzyme. Nature, 380, 82–85.

    Article  CAS  Google Scholar 

  71. Maldonado, E., Shiekhattar, R., Sheldon, M., Cho, H., Drapkin, R., Rickert, P., et al. (1996). A human RNA polymerase II complex associated with SRB and DNA-repair proteins. Nature, 381, 86–89.

    Article  CAS  Google Scholar 

  72. Wilson, C., Chao, D., Imbalzano, A., Schnitzler, G., Kingston, R., & Young, R. (1996). RNA polymerase II holoenzyme contains SWI/SNF regulators involved in chromatin remodeling. Cell, 84, 235–244.

    Article  CAS  Google Scholar 

  73. Parvin, J., & Young, R. (1998). Regulatory targets in the RNA polymerase II holoenzyme. Current Opinion in Genetics and Development, 8, 565–570.

    Article  CAS  Google Scholar 

  74. Martinez, E. (2002). Multi-protein complexes in eukaryotic gene transcription. Plant Molecular Biology, 50, 925–947.

    Article  CAS  Google Scholar 

  75. Dahmus, M. (1996). Reversible phosphorylation of the C-terminal domain of RNA polymerase II. The Journal of Biological Chemistry, 271, 19009–19012.

    CAS  Google Scholar 

  76. Lu, H., Zawel, L., Fisher, L., Egly, J., & Reinberg, D. (1992). Human general transcription factor IIH phosphorylates the C-terminal domain of RNA polymerase II. Nature, 358, 641–645.

    Article  CAS  Google Scholar 

  77. Cisek, L., & Corden, J. (1989). Phosphorylation of RNA polymerase by the murine homologue of the cell-cycle control protein cdc2. Nature, 339, 679–684.

    Article  CAS  Google Scholar 

  78. Liao, S., Zhang, J., Jeffery, D., Koleske, A., Thompson, C., Chao, D., et al. (1995). A kinase-cyclin pair in the RNA polymerase II holoenzyme. Nature, 374, 193–196.

    Article  CAS  Google Scholar 

  79. Marshall, N., Peng, J., Xie, Z., & Price, D. (1996). Control of RNA polymerase II elongation potential by a novel carboxyl-terminal domain kinase. The Journal of Biological Chemistry, 271, 27176–27183.

    Article  CAS  Google Scholar 

  80. Lee, J., & Greenleaf, A. (1991). CTD kinase large subunit is encoded by CTK1, a gene required for normal growth of Saccharomyces cerevisiae. Gene Expression, 1, 149–167.

    CAS  Google Scholar 

  81. Albright, S., & Tjian, R. (2000). TAFs revisited: More data reveal new twists and confirm old ideas. Gene, 242, 1–13.

    Article  CAS  Google Scholar 

  82. Green, M. (2000). TBP-associated factors (TAFIIs): Multiple, selective transcriptional mediators in common complexes. Trends in Biochemical Sciences, 25, 59–63.

    Article  CAS  Google Scholar 

  83. Tora, L. (2002). A unified nomenclature for TATA box binding protein (TBP)-associated factors (TAFs) involved in RNA polymerase II transcription. Genes and Development, 16, 673–675.

    Article  CAS  Google Scholar 

  84. Hochheimer, A., & Tjian, R. (2003). Diversified transcription initiation complexes expand promoter selectivity and tissue-specific gene expression. Genes and Development, 17, 1309–1320.

    Article  CAS  Google Scholar 

  85. Verrijzer, C., & Tjian, R. (1996). TAFs mediate transcriptional activation and promoter selectivity. Trends in Biochemical Sciences, 21, 338–342.

    Article  CAS  Google Scholar 

  86. Wassarman, D., & Sauer, F. (2001). TAF(II)250: A transcription toolbox. Journal of Cell Science, 114, 2895–2902.

    CAS  Google Scholar 

  87. Veenstra, G., & Wolffe, A. (2001). Gene-selective developmental roles of general transcription factors. Trends in Biochemical Sciences, 26, 665–671.

    Article  CAS  Google Scholar 

  88. Pontiller, J., Gross, S., Thaisuchat, H., Hesse, F., & Ernst, W. (2008). Identification of CHO endogenous promoter elements based on a genomic library approach. Molecular Biotechnology, 39, 135–139.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Martina Baumann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baumann, M., Pontiller, J. & Ernst, W. Structure and Basal Transcription Complex of RNA Polymerase II Core Promoters in the Mammalian Genome: An Overview. Mol Biotechnol 45, 241–247 (2010). https://doi.org/10.1007/s12033-010-9265-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12033-010-9265-6

Keywords

Navigation