A high-resolution map of active promoters in the human genome (original) (raw)

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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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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  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

Authors

  1. Tae Hoon Kim
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  2. Leah O. Barrera
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  3. Ming Zheng
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  4. Chunxu Qu
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  5. Michael A. Singer
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  6. Todd A. Richmond
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  7. Yingnian Wu
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  8. Roland D. Green
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  9. Bing Ren
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Correspondence toBing Ren.

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

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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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