Genomic and biochemical insights into the specificity of ETS transcription factors

Peter C. Hollenhorst, Lawrence P. McIntosh, Barbara J. Graves

Research output: Contribution to journalArticle

278 Scopus citations

Abstract

ETS proteins are a group of evolutionarily related, DNA-binding transcriptional factors. These proteins direct gene expression in diverse normal and disease states by binding to specific promoters and enhancers and facilitating assembly of other components of the transcriptional machinery. The highly conserved DNA-binding ETS domain defines the family and is responsible for specific recognition of a common sequence motif, 5′-GGA(A/T)-3′. Attaining specificity for biological regulation in such a family is thus a conundrum. We present the current knowledge of routes to functional diversity and DNA binding specificity, including divergent properties of the conserved ETS and PNT domains, the involvement of flanking structured and unstructured regions appended to these dynamic domains, posttranslational modifications, and protein partnerships with other DNA-binding proteins and coregulators. The review emphasizes recent advances from biochemical and biophysical approaches, as well as insights from genomic studies that detect ETS-factor occupancy in living cells.

Original languageEnglish (US)
Pages (from-to)437-471
Number of pages35
JournalAnnual Review of Biochemistry
Volume80
DOIs
StatePublished - Jul 7 2011

Keywords

  • autoinhibition
  • ChIP-Seq
  • DNA binding
  • ETS domain
  • PNT domain
  • protein dynamics

ASJC Scopus subject areas

  • Biochemistry

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