1. Ludwig Institute for Cancer Research and
2. Department of Cellular and Molecular Medicine and Moores Cancer Center, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA
3. 8125 Math Sciences Building, UCLA Department of Statistics, Los Angeles, California 90095-1554, USA
4. NimbleGen Systems, Inc., 1 Science Court, Madison, Wisconsin 53711, USA
5. *These authors contributed equally to this work

Correspondence to: Bing Ren^1,2 Correspondence and requests for materials should be addressed to B.R. (Email: biren@ucsd.edu). The microarray data sets are available from GEO (Gene Expression Omnibus) under accession number GSE2672, and from http://licr-renlab.ucsd.edu/download.html.

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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