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A high-resolution map of active promoters in the human genome

Nature volume 436, pages 876–880 (2005)Cite this article

Abstract

In eukaryotic cells, transcription of every protein-coding gene begins with the assembly of an RNA polymerase II preinitiation complex (PIC) on the promoter1. The promoters, in conjunction with enhancers, silencers and insulators, define the combinatorial codes that specify gene expression patterns2. Our ability to analyse the control logic encoded in the human genome is currently limited by a lack of accurate information regarding the promoters for most genes3. Here we describe a genome-wide map of active promoters in human fibroblast cells, determined by experimentally locating the sites of PIC binding throughout the human genome. This map defines 10,567 active promoters corresponding to 6,763 known genes and at least 1,196 un-annotated transcriptional units. Features of the map suggest extensive use of multiple promoters by the human genes and widespread clustering of active promoters in the genome. In addition, examination of the genome-wide expression profile reveals four general classes of promoters that define the transcriptome of the cell. These results provide a global view of the functional relationships among transcriptional machinery, chromatin structure and gene expression in human cells.

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Figure 1: Identification and characterization of active promoters in the human genome.
Figure 2: The chromatin-modification features of the active promoters.
Figure 3: Use of multiple promoters by human genes.
Figure 4: Four distinct classes of promoters define the transcriptome of IMR90 cells.

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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)

    Article  CAS  Google Scholar 

  2. Tjian, R. & Maniatis, T. Transcriptional activation: a complex puzzle with few easy pieces. Cell 77, 5–8 (1994)

    Article  CAS  Google Scholar 

  3. Trinklein, N. D., Aldred, S. J., Saldanha, A. J. & Myers, R. M. Identification and functional analysis of human transcriptional promoters. Genome Res. 13, 308–312 (2003)

    Article  CAS  Google Scholar 

  4. Reinberg, D. et al. The RNA polymerase II general transcription factors: past, present, and future. Cold Spring Harb. Symp. Quant. Biol. 63, 83–103 (1998)

    Article  CAS  Google Scholar 

  5. Ren, B. et al. Genome-wide location and function of DNA binding proteins. Science 290, 2306–2309 (2000)

    Article  ADS  CAS  Google Scholar 

  6. Kim, T. H. et al. Direct isolation and identification of promoters in the human genome. Genome Res. 15, 830–839 (2005)

    Article  CAS  Google Scholar 

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

    Article  ADS  Google Scholar 

  8. Singh-Gasson, S. et al. Maskless fabrication of light-directed oligonucleotide microarrays using a digital micromirror array. Nature Biotechnol. 17, 974–978 (1999)

    Article  CAS  Google Scholar 

  9. Ruppert, S., Wang, E. H. & Tjian, R. Cloning and expression of human TAFII250: a TBP-associated factor implicated in cell-cycle regulation. Nature 362, 175–179 (1993)

    Article  ADS  CAS  Google Scholar 

  10. Suzuki, Y., Yamashita, R., Sugano, S. & Nakai, K. DBTSS, DataBase of Transcriptional Start Sites: progress report 2004. Nucleic Acids Res. 32 (database issue), D78–81 (2004)

    Article  CAS  Google Scholar 

  11. Pruitt, K. D., Tatusova, T. & Maglott, D. R. NCBI Reference Sequence project: update and current status. Nucleic Acids Res. 31, 34–37 (2003)

    Article  CAS  Google Scholar 

  12. Benson, D. A., Karsch-Mizrachi, I., Lipman, D. J., Ostell, J. & Wheeler, D. L. GenBank: update. Nucleic Acids Res. 32 (database issue)), D23–26 (2004)

    Article  CAS  Google Scholar 

  13. Birney, E. et al. Ensembl 2004. Nucleic Acids Res. 32 (database issue), D468–470 (2004)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  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. Schubeler, D. et al. The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. Genes Dev. 18, 1263–1271 (2004)

    Article  Google Scholar 

  17. Griffiths-Jones, S. The microRNA Registry. Nucleic Acids Res. 32 (database issue), D109–111 (2004)

    Article  CAS  Google Scholar 

  18. International Human Genome Sequencing Consortium, Finishing the euchromatic sequence of the human genome. Nature 431, 931–945 (2004)

    Article  ADS  Google Scholar 

  19. Bertone, P. et al. Global identification of human transcribed sequences with genome tiling arrays. Science 306, 2242–2246 (2004)

    Article  ADS  CAS  Google Scholar 

  20. 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  Google Scholar 

  21. Saha, S. et al. Using the transcriptome to annotate the genome. Nature Biotechnol. 20, 508–512 (2002)

    Article  CAS  Google Scholar 

  22. Rinn, J. L. et al. The transcriptional activity of human chromosome 22. Genes Dev. 17, 529–540 (2003)

    Article  CAS  Google Scholar 

  23. Su, A. I. et al. Large-scale analysis of the human and mouse transcriptomes. Proc. Natl Acad. Sci. USA 99, 4465–4470 (2002)

    Article  ADS  CAS  Google Scholar 

  24. Spellman, P. T. & Rubin, G. M. Evidence for large domains of similarly expressed genes in the Drosophila genome. J. Biol. 1, 5 (2002)

    Article  Google Scholar 

  25. Roy, P. J., Stuart, J. M., Lund, J. & Kim, S. K. Chromosomal clustering of muscle-expressed genes in Caenorhabditis elegans. Nature 418, 975–979 (2002)

    Article  ADS  CAS  Google Scholar 

  26. Caron, H. et al. The human transcriptome map: clustering of highly expressed genes in chromosomal domains. Science 291, 1289–1292 (2001)

    Article  ADS  CAS  Google Scholar 

  27. Maniatis, T. & Reed, R. An extensive network of coupling among gene expression machines. Nature 416, 499–506 (2002)

    Article  ADS  CAS  Google Scholar 

  28. Krumm, A., Hickey, L. B. & Groudine, M. Promoter-proximal pausing of RNA polymerase II defines a general rate-limiting step after transcription initiation. Genes Dev. 9, 559–572 (1995)

    Article  CAS  Google Scholar 

  29. Ambros, V. The functions of animal microRNAs. Nature 431, 350–355 (2004)

    Article  ADS  CAS  Google Scholar 

  30. Yuh, C. H., Bolouri, H. & Davidson, E. H. Genomic cis-regulatory logic: experimental and computational analysis of a sea urchin gene. Science 279, 1896–1902 (1998)

    Article  ADS  CAS  Google Scholar 

Download references

Acknowledgements

We thank J. Kadonaga, R. A. Young, R. Kolodner, W. K. Cavenee, S. Van Calcar and C. K. Glass for discussion and comments on the manuscript. This research was supported by a Ruth L. Kirschstein National Research Service Award (T.H.K.) a Ford Foundation Predoctoral Fellowship (L.O.B.); the Ludwig Institute for Cancer Research (B.R.); NIH grants (B.R.) and the NSF (Y.W.). Author Contributions B.R. and T.H.K. conceived the experimental design; T.H.K. performed the experiments; data analysis was by L.O.B. and C.Q.; microarray fabrication, hybridization and data acquisition were by M.A.S., T.A.R. and R.D.G.; M.Z. and Y.W. worked on the computational peak detection program; writing of the manuscript was primarily by T.H.K. and B.R.

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Author notes

  1. Tae Hoon Kim and Leah O. Barrera: *These authors contributed equally to this work

Authors and Affiliations

  1. Ludwig Institute for Cancer Research,

    Tae Hoon Kim, Leah O. Barrera, Chunxu Qu & Bing Ren

  2. Department of Cellular and Molecular Medicine and Moores Cancer Center, UCSD School of Medicine, 9500 Gilman Drive, California, 92093-0653, La Jolla, USA

    Bing Ren

  3. 8125 Math Sciences Building, UCLA Department of Statistics, California, 90095-1554, Los Angeles, USA

    Ming Zheng & Yingnian Wu

  4. NimbleGen Systems, Inc., 1 Science Court, Wisconsin, 53711, Madison, USA

    Michael A. Singer, Todd A. Richmond & Roland D. Green

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Corresponding author

Correspondence to Bing Ren.

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Competing interests

R.D.G., M.A.S. and T.A.R. work for NimbleGen Systems, Inc., which may profit from the publication of this paper.

Supplementary information

Supplementary Notes

The file contains Supplementary Methods and legends for Supplementary Figures and Supplementary Tables. (DOC 189 kb)

Supplementary Figures S1-S6

The file contains six Supplemental Figures in order that accompany the manuscript. The legends for these figures are included in the Supplementary Notes. (PDF 5095 kb)

Supplementary Table S1

9,328 TAF1 binding sites matched to known 5 ends (XLS 2503 kb)

Supplementary Table S2

1,239 putative promoters (Acembly-match and no 5 end match). (XLS 227 kb)

Supplementary Table S3

Validation of putative promoters. (XLS 185 kb)

Supplementary Table S4

Multiple promoter usage. (XLS 317 kb)

Supplementary Table S5

Clusters of genes with TAF1-bound promoters. (XLS 59 kb)

Supplementary Table S6

Gene expression classes. (XLS 1124 kb)

Supplementary Table S7

Histone modification on class III and IV genes. (XLS 46 kb)

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Kim, T., Barrera, L., Zheng, M. et al. A high-resolution map of active promoters in the human genome. Nature 436, 876–880 (2005). https://doi.org/10.1038/nature03877

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