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

Peter C. Hollenhorst, Atul A. Shah, Christopher Hopkins, Barbara J. Graves

Research output: Contribution to journalArticle

214 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1882-1894
Number of pages13
JournalGenes and Development
Volume21
Issue number15
DOIs
StatePublished - Aug 1 2007

Keywords

  • ChIP-chip
  • Cooperative binding
  • ETS
  • Gene families
  • Promoter specificity
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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