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Estimating binding properties of transcription factors from genome-wide binding profiles

Zabet, Nicolae Radu and Adryan, Boris (2015) 'Estimating binding properties of transcription factors from genome-wide binding profiles.' Nucleic Acids Research, 43 (1). pp. 84-94. ISSN 0305-1048

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The binding of transcription factors (TFs) is essential for gene expression. One important characteristic is the actual occupancy of a putative binding site in the genome. In this study, we propose an analytical model to predict genomic occupancy that incorporates the preferred target sequence of a TF in the form of a position weight matrix (PWM), DNA accessibility data (in the case of eukaryotes), the number of TF molecules expected to be bound specifically to the DNA and a parameter that modulates the specificity of the TF. Given actual occupancy data in the form of ChIP-seq profiles, we backwards inferred copy number and specificity for five Drosophila TFs during early embryonic development: Bicoid, Caudal, Giant, Hunchback and Kruppel. Our results suggest that these TFs display thousands of molecules that are specifically bound to the DNA and that whilst Bicoid and Caudal display a higher specificity, the other three TFs (Giant, Hunchback and Kruppel) display lower specificity in their binding (despite having PWMs with higher information content). This study gives further weight to earlier investigations into TF copy numbers that suggest a significant proportion of molecules are not bound specifically to the DNA.

Item Type: Article
Uncontrolled Keywords: Cell Nucleus; Animals; Drosophila melanogaster; Transcription Factors; DNA; Genomics; Binding Sites; Protein Binding; Regulatory Elements, Transcriptional; Position-Specific Scoring Matrices
Subjects: Q Science > QC Physics
Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 21 Oct 2015 10:14
Last Modified: 18 Aug 2022 12:10

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