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

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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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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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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