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  • Review Article
  • Published:

Mammalian RNA polymerase II core promoters: insights from genome-wide studies

Nature Reviews Genetics volume 8, pages 424–436 (2007)Cite this article

Key Points

  • Genome-wide methods have identified fivefold to tenfold more transcription start sites (TSSs) than were previously known to exist. Many of these occur at unexpected locations, such as assumed gene deserts, exons and 3′ UTRs of known genes.

  • Most promoters are not represented by the accepted model of a single TSS with an upstream TATA-box; a cluster of TSSs in a narrow region of genomic DNA is the most common pattern. Core promoters can be classified according to the distribution and relative usage of their TSSs.

  • The TSS distribution of core promoters is tightly coupled to the occurrence of both known cis-regulatory elements and gene function, and is generally conserved between humans and mice.

  • Few promoters use an extended initiator sequence to define the TSS. The most consistent pattern is a pyrimidine–purine dinucleotide that overlaps the TSS.

  • Most genes have at least two distinct promoters, which may be differentially regulated and generate mRNAs that encode different protein isoforms.

  • The wealth of TSS data enables new types of analysis, including the study of promoter evolution and functional analysis of promoters on a genome-wide scale.

Abstract

The identification and characterization of mammalian core promoters and transcription start sites is a prerequisite to understanding how RNA polymerase II transcription is controlled. New experimental technologies have enabled genome-wide discovery and characterization of core promoters, revealing that most mammalian genes do not conform to the simple model in which a TATA box directs transcription from a single defined nucleotide position. In fact, most genes have multiple promoters, within which there are multiple start sites, and alternative promoter usage generates diversity and complexity in the mammalian transcriptome and proteome. Promoters can be described by their start site usage distribution, which is coupled to the occurrence of cis-regulatory elements, gene function and evolutionary constraints. A comprehensive survey of mammalian promoters is a major step towards describing and understanding transcriptional control networks.

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Figure 1: TSS classes in mammalian promoters.
Figure 2: DNA motif predictions in core promoters depends on TSS architecture.
Figure 3: Complex TSS distributions within exons.

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References

  1. Smale, S. T. & Kadonaga, J. T. The RNA polymerase II core promoter. Annu. Rev. Biochem. 72, 449–479 (2003). An excellent in-depth review of well-studied core promoter elements.

    Article  CAS  PubMed  Google Scholar 

  2. Gross, P. & Oelgeschlager, T. Core promoter-selective RNA polymerase II transcription. Biochem. Soc. Symp. 2006, 225–236 (2006).

    Article  Google Scholar 

  3. Hampsey, M. Molecular genetics of the RNA polymerase II general transcriptional machinery. Microbiol. Mol. Biol. Rev. 62, 465–503 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Thomas, M. C. & Chiang, C. M. The general transcription machinery and general cofactors. Crit. Rev. Biochem. Mol. Biol. 41, 105–178 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Lewis, B. A. & Reinberg, D. The mediator coactivator complex: functional and physical roles in transcriptional regulation. J. Cell Sci. 116, 3667–3675 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Black, J. C., Choi, J. E., Lombardo, S. R. & Carey, M. A mechanism for coordinating chromatin modification and preinitiation complex assembly. Mol. Cell 23, 809–818 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Kadonaga, J. T. Regulation of RNA polymerase II transcription by sequence-specific DNA binding factors. Cell 116, 247–257 (2004).

    Article  CAS  PubMed  Google Scholar 

  8. Wasserman, W. W. & Sandelin, A. Applied Bioinformatics for the identification of regulatory elements. Nature Rev. Genet. 5, 276–287 (2004). Reviews the computational methods that underlie the prediction of promoter positions and transcription factor binding sites, targeted towards bench biologists.

    Article  CAS  PubMed  Google Scholar 

  9. Bajic, V. B., Tan, S. L., Suzuki, Y. & Sugano, S. Promoter prediction analysis on the whole human genome. Nature Biotechnol. 22, 1467–1473 (2004).

    Article  CAS  Google Scholar 

  10. Brodsky, A. S. et al. Genomic mapping of RNA polymerase II reveals sites of co-transcriptional regulation in human cells. Genome Biol. 6, R64 (2005). This study revealed the surprisingly high concentration of RNApolII that is bound to exons but not introns.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kim, T. H. et al. A high-resolution map of active promoters in the human genome. Nature 436, 876–880 (2005). The first genome-wide ChIP–chip determination using antibodies that targeted the PIC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gershenzon, N. I. & Ioshikhes, I. P. Synergy of human Pol II core promoter elements revealed by statistical sequence analysis. Bioinformatics 21, 1295–1300 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Ohler, U. Identification of core promoter modules in Drosophila and their application in accurate transcription start site prediction. Nucleic Acids Res. 34, 5943–5950 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ohler, U., Liao, G. C., Niemann, H. & Rubin, G. M. Computational analysis of core promoters in the Drosophila genome. Genome Biol. 3, RESEARCH0087 (2002).

  16. Molina, C. & Grotewold, E. Genome wide analysis of Arabidopsis core promoters. BMC Genomics 6, 25 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schug, J. et al. Promoter features related to tissue specificity as measured by Shannon entropy. Genome Biol. 6, R33 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cawley, S. et al. Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 116, 499–509 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Cheng, J. et al. Transcriptional maps of 10 human chromosomes at 5-nucleotide resolution. Science 308, 1149–1154 (2005).

    Article  CAS  PubMed  Google Scholar 

  20. Crawford, G. E. et al. DNase-chip: a high-resolution method to identify DNase I hypersensitive sites using tiled microarrays. Nature Methods 3, 503–509 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fan, J. B., Chee, M. S. & Gunderson, K. L. Highly parallel genomic assays. Nature Rev. Genet. 7, 632–644 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Kapranov, P. et al. Large-scale transcriptional activity in chromosomes 21 and 22. Science 296, 916–919 (2002). One of several key publications from Affymetrix on the utility of tiling arrays and the widespread occurrence of non-coding RNA.

    Article  CAS  PubMed  Google Scholar 

  23. Carninci, P. et al. The transcriptional landscape of the mammalian genome. Science 309, 1559–1563 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Carninci, P. et al. Genome-wide analysis of mammalian promoter architecture and evolution. Nature Genet. (2006). The largest experimental promoter identification study to date in any species, with subsequent computational analysis.

  25. Harbers, M. & Carninci, P. Tag-based approaches for transcriptome research and genome annotation. Nature Methods 2, 495–502 (2005).

    Article  CAS  PubMed  Google Scholar 

  26. Barrera, L. O. & Ren, B. The transcriptional regulatory code of eukaryotic cells — insights from genome-wide analysis of chromatin organization and transcription factor binding. Curr. Opin. Cell Biol. 18, 291–298 (2006).

    Article  CAS  PubMed  Google Scholar 

  27. Kimura, K. et al. Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome Res. 16, 55–65 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Carninci, P. et al. Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia. Genome Res. 13, 1273–1289 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Suzuki, Y. et al. Large-scale collection and characterization of promoters of human and mouse genes. In silico Biol. 4, 0036 (2004).

    Google Scholar 

  30. Shiraki, T. et al. Cap analysis gene expression for high-throughput analysis of transcriptional starting point and identification of promoter usage. Proc. Natl Acad. Sci. USA 100, 15776–15781 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kodzius, R. et al. CAGE: cap analysis of gene expression. Nature Methods 3, 211–222 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. Hashimoto, S. et al. 5′-end SAGE for the analysis of transcriptional start sites. Nature Biotechnol. 22, 1146–1149 (2004).

    Article  CAS  Google Scholar 

  33. Wei, C. L. et al. 5′ long serial analysis of gene expression (LongSAGE) and 3′ LongSAGE for transcriptome characterization and genome annotation. Proc. Natl Acad. Sci. USA 101, 11701–11706 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ng, P. et al. Gene identification signature (GIS) analysis for transcriptome characterization and genome annotation. Nature Methods 2, 105–111 (2005).

    Article  CAS  PubMed  Google Scholar 

  35. Shannon, M. F. & Rao, S. Transcription. Of chips and ChIPs. Science 296, 666–669 (2002).

    Article  CAS  PubMed  Google Scholar 

  36. Ren, B. & Dynlacht, B. D. Use of chromatin immunoprecipitation assays in genome-wide location analysis of mammalian transcription factors. Methods Enzymol. 376, 304–315 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Loh, Y. H. et al. The OCT4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nature Genet. 38, 431–440 (2006).

    Article  CAS  PubMed  Google Scholar 

  38. Wei, C. L. et al. A global map of p53 transcription-factor binding sites in the human genome. Cell 124, 207–219 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. Kampa, D. et al. Novel RNAs identified from an in-depth analysis of the transcriptome of human chromosomes 21 and 22. Genome Res. 14, 331–342 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Schaefer, B. C. Revolutions in rapid amplification of cDNA ends: new strategies for polymerase chain reaction cloning of full-length cDNA ends. Anal. Biochem. 227, 255–273 (1995).

    Article  CAS  PubMed  Google Scholar 

  41. Okazaki, Y. et al. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420, 563–573 (2002).

    Article  PubMed  Google Scholar 

  42. Yamashita, R. et al. DBTSS: DataBase of Human Transcription Start Sites, progress report 2006. Nucleic Acids Res. 34, D86–D89 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Jackson, D. A., Pombo, A. & Iborra, F. The balance sheet for transcription: an analysis of nuclear RNA metabolism in mammalian cells. Faseb J. 14, 242–254 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. Kovalskaya, E., Buzdin, A., Gogvadze, E., Vinogradova, T. & Sverdlov, E. Functional human endogenous retroviral LTR transcription start sites are located between the R and U5 regions. Virology 346, 373–378 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. Buzdin, A., Kovalskaya-Alexandrova, E., Gogvadze, E. & Sverdlov, E. GREM, a technique for genome-wide isolation and quantitative analysis of promoter active repeats. Nucleic Acids Res. 34, e67 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ling, J., Baibakov, B., Pi, W., Emerson, B. M. & Tuan, D. The HS2 enhancer of the β-globin locus control region initiates synthesis of non-coding, polyadenylated RNAs independent of a cis-linked globin promoter. J. Mol. Biol. 350, 883–896 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Drewell, R. A. et al. Novel conserved elements upstream of the H19 gene are transcribed and act as mesodermal enhancers. Development 129, 1205–1213 (2002).

    CAS  PubMed  Google Scholar 

  48. Ravasi, T. & Hume, D. A. in Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics (ed. Subramamiam, S.) (John Wiley & Sons, Chichester, 2005).

    Google Scholar 

  49. Gingeras, T. R. The multitasking genome. Nature Genet. 38, 608–609 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Suzuki, Y. et al. Diverse transcriptional initiation revealed by fine, large-scale mapping of mRNA start sites. EMBO Rep. 2, 388–393 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ponjavic, J. et al. Transcriptional and structural impact of TATA-initiation site spacing in mammalian core promoters. Genome Biol. 7, R78 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Hahn, S. Structure and mechanism of the RNA polymerase II transcription machinery. Nature Struct. Mol. Biol. 11, 394–403 (2004).

    Article  CAS  Google Scholar 

  53. Zhu, Q., Dabi, T. & Lamb, C. TATA box and initiator functions in the accurate transcription of a plant minimal promoter in vitro. Plant Cell 7, 1681–1689 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. O'Shea-Greenfield, A. & Smale, S. T. Roles of TATA and initiator elements in determining the start site location and direction of RNA polymerase II transcription. J. Biol. Chem. 267, 1391–1402 (1992).

    CAS  PubMed  Google Scholar 

  55. Grace, M. L., Chandrasekharan, M. B., Hall, T. C. & Crowe, A. J. Sequence and spacing of TATA box elements are critical for accurate initiation from the β-phaseolin promoter. J. Biol. Chem. 279, 8102–8110 (2004).

    Article  CAS  PubMed  Google Scholar 

  56. Smale, S. T. et al. The initiator element: a paradigm for core promoter heterogeneity within metazoan protein-coding genes. Cold Spring Harb. Symp. Quant. Biol. 63, 21–31 (1998).

    Article  CAS  PubMed  Google Scholar 

  57. Weis, L. & Reinberg, D. Accurate positioning of RNA polymerase II on a natural TATA-less promoter is independent of TATA-binding-protein-associated factors and initiator-binding proteins. Mol. Cell. Biol. 17, 2973–2984 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Gallagher, P. G. et al. A dinucleotide deletion in the ankyrin promoter alters gene expression, transcription initiation and TFIID complex formation in hereditary spherocytosis. Hum. Mol. Genet. 14, 2501–2509 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. Lee, M. P. et al. ATG deserts define a novel core promoter subclass. Genome Res. 15, 1189–1197 (2005). An in-depth experimental study of promoters with multiple start sites, followed by a computational screening of ATG deserts in the human genome.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Carcamo, J., Buckbinder, L. & Reinberg, D. The initiator directs the assembly of a transcription factor IID-dependent transcription complex. Proc. Natl Acad. Sci. USA 88, 8052–8056 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Luger, K., Mader, A. W., Richmond, R. K., Sargent, D. F. & Richmond, T. J. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389, 251–260 (1997).

    Article  CAS  PubMed  Google Scholar 

  62. Nishida, H. et al. Histone H3 acetylated at lysine 9 in promoter is associated with low nucleosome density in the vicinity of transcription start site in human cell. Chromosome Res. 14, 203–211 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Mellor, J. Dynamic nucleosomes and gene transcription. Trends Genet. 22, 320–329 (2006).

    Article  CAS  PubMed  Google Scholar 

  64. Bantignies, F. & Cavalli, G. Cellular memory and dynamic regulation of polycomb group proteins. Curr. Opin. Cell Biol. 18, 275–283 (2006).

    Article  CAS  PubMed  Google Scholar 

  65. Segal, E. et al. A genomic code for nucleosome positioning. Nature 442, 772–778 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kawaji, H. et al. Dynamic usage of transcription start sites within core promoters. Genome Biol. 7, R118 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Taylor, M. S. et al. Heterotachy in mammalian promoter evolution. PLoS Genet. 2, e30 (2006). The most comprehensive study of promoter evolution in mammalian species to date.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Albig, W., Kioschis, P., Poustka, A., Meergans, K. & Doenecke, D. Human histone gene organization: nonregular arrangement within a large cluster. Genomics 40, 314–322 (1997).

    Article  CAS  PubMed  Google Scholar 

  69. Guarguaglini, G. et al. Expression of the murine RanBP1 and Htf9-c genes is regulated from a shared bidirectional promoter during cell cycle progression. Biochem. J. 325, 277–286 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sugimoto, M., Oohashi, T. & Ninomiya, Y. The genes COL4A5 and COL4A6, coding for basement membrane collagen chains {alpha}5(IV) and {alpha}6(IV), are located head-to-head in close proximity on human chromosome Xq22 and COL4A6 is transcribed from two alternative promoters. Proc. Natl Acad. Sci. USA 91, 11679–11683 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Trinklein, N. D. et al. An abundance of bidirectional promoters in the human genome. Genome Res. 14, 62–66 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Engstrom, P. G. et al. Complex loci in human and mouse genomes. PLoS Genet. 2, e47 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Katayama, S. et al. Antisense transcription in the mammalian transcriptome. Science 309, 1564–1566 (2005).

    Article  PubMed  Google Scholar 

  74. Pruitt, K. D., Tatusova, T. & Maglott, D. R. NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res. 33, D501–D504 (2005).

    Article  CAS  PubMed  Google Scholar 

  75. Bai, L., Santangelo, T. J. & Wang, M. D. Single-molecule analysis of RNA polymerase transcription. Annu. Rev. Biophys. Biomol. Struct. 35, 343–360 (2006).

    Article  CAS  PubMed  Google Scholar 

  76. Kornblihtt, A. R., de la Mata, M., Fededa, J. P., Munoz, M. J. & Nogues, G. Multiple links between transcription and splicing. RNA 10, 1489–1498 (2004). An excellent review that connects the splicing process to transcription.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Dye, M. J., Gromak, N. & Proudfoot, N. J. Exon tethering in transcription by RNA polymerase II. Mol. Cell 21, 849–859 (2006).

    Article  CAS  PubMed  Google Scholar 

  78. Schwartz, S. et al. Human–mouse alignments with BLASTZ. Genome Res. 13, 103–107 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Keightley, P. D., Lercher, M. J. & Eyre-Walker, A. Evidence for widespread degradation of gene control regions in hominid genomes. PLoS. Biol. 3, e42 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lee, S., Kohane, I. & Kasif, S. Genes involved in complex adaptive processes tend to have highly conserved upstream regions in mammalian genomes. BMC Genomics 6, 168 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Tirosh, I., Weinberger, A., Carmi, M. & Barkai, N. A genetic signature of interspecies variations in gene expression. Nature Genet. 38, 830–834 (2006).

    Article  CAS  PubMed  Google Scholar 

  82. Nilsson, R. et al. Transcriptional network dynamics in macrophage activation. Genomics 88, 133–142 (2006).

    Article  CAS  PubMed  Google Scholar 

  83. Yan, C. & Boyd, D. D. Histone H3 acetylation and H3 K4 methylation define distinct chromatin regions permissive for transgene expression. Mol. Cell. Biol. 26, 6357–6371 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Pokholok, D. K. et al. Genome-wide map of nucleosome acetylation and methylation in yeast. Cell 122, 517–527 (2005).

    Article  CAS  PubMed  Google Scholar 

  85. Wiren, M. et al. Genomewide analysis of nucleosome density histone acetylation and HDAC function in fission yeast. EMBO J. 24, 2906–2918 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Guccione, E. et al. Myc-binding-site recognition in the human genome is determined by chromatin context. Nature Cell Biol. 8, 764–770 (2006).

    Article  CAS  PubMed  Google Scholar 

  87. Furuno, M. et al. Clusters of internally primed transcripts reveal novel long noncoding RNAs. PLoS Genet. 2, e37 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wurtele, H. & Chartrand, P. Genome-wide scanning of HoxB1-associated loci in mouse ES cells using an open-ended chromosome conformation capture methodology. Chromosome Res. 14, 477–495 (2006).

    Article  CAS  PubMed  Google Scholar 

  89. Murrell, A., Heeson, S. & Reik, W. Interaction between differentially methylated regions partitions the imprinted genes Igf2 and H19 into parent-specific chromatin loops. Nature Genet. 36, 889–893 (2004).

    Article  CAS  PubMed  Google Scholar 

  90. Chakalova, L., Debrand, E., Mitchell, J. A., Osborne, C. S. & Fraser, P. Replication and transcription: shaping the landscape of the genome. Nature Rev. Genet 6, 669–677 (2005).

    Article  CAS  PubMed  Google Scholar 

  91. Krivan, W. & Wasserman, W. W. A predictive model for regulatory sequences directing liver-specific transcription. Genome Res. 11, 1559–1566 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Lenhard, B. et al. Identification of conserved regulatory elements by comparative genome analysis. J. Biol. 2, 13 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Margulies, M. et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437, 376–380 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ng, P. et al. Multiplex sequencing of paired-end ditags (MS-PET): a strategy for the ultra-high-throughput analysis of transcriptomes and genomes. Nucleic Acids Res. 34, e84 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Sabo, P. J. et al. Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays. Nature Methods 3, 511–518 (2006).

    Article  CAS  PubMed  Google Scholar 

  96. ENCODE Project Consortium. The ENCODE (ENCyclopedia Of DNA Elements) Project. Science 306, 636–640 (2004).

  97. Sambrook, J. & Russel, D. W. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2001).

    Google Scholar 

  98. Kadonaga, J. T. The DPE, a core promoter element for transcription by RNA polymerase II. Exp. Mol. Med. 34, 259–264 (2002).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Gardiner-Garden, M. & Frommer, M. CpG islands in vertebrate genomes. J. Mol. Biol. 196, 261–282 (1987).

    Article  CAS  PubMed  Google Scholar 

  101. Antequera, F. & Bird, A. Number of CpG islands and genes in human and mouse. Proc. Natl Acad. Sci. USA 90, 11995–11999 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Saxonov, S., Berg, P. & Brutlag, D. L. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc. Natl Acad. Sci. USA 103, 1412–1417 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Gustincich, S. et al. The complexity of the mammalian transcriptome. J. Physiol. 575, 321–332 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Altschul, S. F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Hinrichs, A. S. et al. The UCSC Genome Browser Database: update 2006. Nucleic Acids Res. 34, D590–D598 (2006).

    Article  CAS  PubMed  Google Scholar 

  106. Harrow, J. et al. GENCODE: producing a reference annotation for ENCODE. Genome Biol. 7, S41–S49 (2006).

    Article  Google Scholar 

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Authors and Affiliations

  1. ARC Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD, 4072, Australia

    David A. Hume

  2. Department of Molecular Biology & Biotech Research and Innovation Centre, The Bioinformatics Centre, Ole Maaløes Vej 5, København Ø, DK-2100, Denmark

    Albin Sandelin

  3. Genome Exploration Research Group (Genome Network Project Core Group), RIKEN Genomic Sciences Center (GSC), RIKEN Yokohama Institute, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Kanagawa, Japan

    Albin Sandelin, Piero Carninci & Yoshihide Hayashizaki

  4. Genome Science Laboratory, Discovery and Research Institute, RIKEN Wako Institute, 2-1 Hirosawa, Wako, 351-0198, Saitama, Japan

    Piero Carninci & Yoshihide Hayashizaki

  5. Computational Biology Unit, Bergen Center for Computational Science, and Sars International Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgate 55, Bergen, N-5008, Norway

    Boris Lenhard

  6. Department of Physiology, MRC Functional Genetics Unit, Anatomy and Genetics, University of Oxford, Oxford, OX1 3QX, United Kingdom

    Jasmina Ponjavic

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FURTHER INFORMATION

CAGE Basic Viewer

CAGE Analysis Viewer

FANTOM3

Database of Transcriptional Start Sites (DBTSS)

Eukaryotic promoter database (EPD)

UCSC ENCODE browser

Glossary

Transcription start site

A nucleotide in the genome that is the first to be transcribed into a particular RNA.

Core promoter

The genomic region that surrounds a TSS or cluster of TSSs. There is no absolute definition for the length of a core promoter; it is generally defined empirically as the segment of DNA that is required to recruit the transcription initiation complex and initiate transcription, given the appropriate external signals (such as enhancers).

Orthologues

Genes that originate from the same ancestral gene and are diverged by a speciation event.

Mediator complex

A multi-subunit complex that can respond to many different activators (such as DNA-bound transcription factors) and links such signals to the core promoter and the transcription machinery.

Tag library

A tag library is similar to a conventional cDNA library, except that, subsequently to isolation and cloning of the cDNA, small fragments are generated by restriction-enzyme cleavage, concatamerized and recloned. This approach enables efficient DNA sequencing of thousands of tags from a single library.

Tag cluster

This Review defines tag clusters as genomic regions in which two or more tags (of 20 nucleotides in length) overlap each other (both being mapped to the same strand).

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Sandelin, A., Carninci, P., Lenhard, B. et al. Mammalian RNA polymerase II core promoters: insights from genome-wide studies. Nat Rev Genet 8, 424–436 (2007). https://doi.org/10.1038/nrg2026

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