Genome-wide analyses reveal properties of redundant and specific promoter occupancy within the ETS gene family.
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.
Hollenhorst
Peter C
PC
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.
Shah
Atul A
AA
Hopkins
Christopher
C
Graves
Barbara J
BJ
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D016384:Consensus Sequence; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015894:Genome, Human; D006801:Humans; D019169:Jurkat Cells; D005810:Multigene Family; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics* / Q000378:metabolism; D011519:Proto-Oncogenes; D013601:T-Lymphocytes / Q000378:metabolism
D050676:Core Binding Factor Alpha 2 Subunit; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D050783:Proto-Oncogene Proteins c-ets; C493728:RUNX1 protein, human; D004247:DNA