A mixture model-based discriminate analysis for identifying ordered transcription factor binding site pairs in gene promoters directly regulated by estrogen receptor-alpha

Bioinformatics. 2006 Sep 15;22(18):2210-6. doi: 10.1093/bioinformatics/btl329. Epub 2006 Jun 29.

Abstract

Motivation: To detect and select patterns of transcription factor binding sites (TFBSs) which distinguish genes directly regulated by estrogen receptor-alpha (ERalpha), we developed an innovative mixture model-based discriminate analysis for identifying ordered TFBS pairs.

Results: Biologically, our proposed new algorithm clearly suggests that TFBSs are not randomly distributed within ERalpha target promoters (P-value < 0.001). The up-regulated targets significantly (P-value < 0.01) possess TFBS pairs, (DBP, MYC), (DBP, MYC/MAX heterodimer), (DBP, USF2) and (DBP, MYOGENIN); and down-regulated ERalpha target genes significantly (P-value < 0.01) possess TFBS pairs, such as (DBP, c-ETS1-68), (DBP, USF2) and (DBP, MYOGENIN). Statistically, our proposed mixture model-based discriminate analysis can simultaneously perform TFBS pattern recognition, TFBS pattern selection, and target class prediction; such integrative power cannot be achieved by current methods.

Availability: The software is available on request from the authors.

Contact: [email protected]

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms*
  • Base Pairing / genetics
  • Base Sequence
  • Binding Sites
  • Computer Simulation
  • Discriminant Analysis
  • Estrogen Receptor alpha / chemistry
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor alpha / metabolism
  • Gene Expression Regulation / genetics*
  • Models, Chemical
  • Models, Genetic*
  • Models, Molecular
  • Models, Statistical
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics*
  • Protein Binding
  • Sequence Alignment / methods
  • Sequence Analysis, DNA / methods*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Estrogen Receptor alpha
  • Transcription Factors