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Genome-wide analyses reveal properties of redundant and specific promoter occupancy within the ETS gene family

¹ Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA; ² Agilent Technologies, Santa Clara, California 95051, USA

The conservation of in vitro DNA-binding properties within families of transcription factors presents a challenge for achieving in vivo specificity. To uncover the mechanisms regulating specificity within the ETS gene family, we have used chromatin immunoprecipitation coupled with genome-wide promoter microarrays to query the occupancy of three ETS proteins in a human T-cell line. Unexpectedly, redundant occupancy was frequently detected, while specific occupancy was less likely. Redundant binding correlated with housekeeping classes of genes, whereas specific binding examples represented more specialized genes. Bioinformatics approaches demonstrated that redundant binding correlated with consensus ETS-binding sequences near transcription start sites. In contrast, specific binding sites diverged dramatically from the consensus and were found further from transcription start sites. One route to specificity was found—a highly divergent binding site that facilitates ETS1 and RUNX1 cooperative DNA binding. The specific and redundant DNA-binding modes suggest two distinct roles for members of the ETS transcription factor family.

[Keywords: ETS; transcription; gene families; cooperative binding; promoter specificity; ChIP–chip]

Received April 16, 2007; revised version accepted June 14, 2007.

E-MAIL barbara.graves{at}hci.utah.edu; FAX (801) 585-1980.

Supplemental material is available at www.genesdev.org.

Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1561707

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