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Local sequence features that influence AP-1 cis-regulatory activity.

Hemangi G Chaudhari1,2, Barak A Cohen1,2

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Most transcription factor binding sites (TFBS) lack regulatory activity. Flanking sequences near Activator Protein 1 (AP-1) binding sites in enhancers distinguish functional from non-functional sites.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • Most transcription factor binding sites (TFBS) in the genome are non-functional.
  • Flanking sequences may hold critical information to differentiate functional TFBS from non-functional ones.

Purpose of the Study:

  • Investigate the role of flanking sequences in the regulatory activity of Activator Protein 1 (AP-1) binding sites.
  • Determine how sequence features adjacent to AP-1 motifs influence their cis-regulatory function within enhancers.

Main Methods:

  • Analyzed sequence features adjacent to AP-1 binding sites within DNase I Hypersensitive Sites (DHS) and enhancer regions.
  • Developed computational models to predict AP-1 site activity based on sequence data.
  • Assessed the impact of mutations on AP-1 core sites and flanking sequences.

Main Results:

  • Sequence features flanking AP-1 core motifs differentiate high-activity from low-activity sites.
  • Adjacent motifs for other transcription factors (TFs) and extended AP-1 motifs contribute to functional specificity.
  • Computational models accurately distinguished AP-1 site activity and predicted effects of mutations.

Conclusions:

  • Extended AP-1 binding sites and adjacent TF binding sites encode information critical for TFBS activity.
  • Understanding flanking sequences is essential for deciphering the regulatory logic of the genome.