Identification of mammalian transcription factors that bind to inaccessible chromatin

Author:

Pop Romana T12,Pisante Alessandra13,Nagy Dorka14,Martin Patrick C N1,Mikheeva Liudmila A1,Hayat Ateequllah5,Ficz Gabriella6,Zabet Nicolae Radu13ORCID

Affiliation:

1. School of Life Sciences, University of Essex , Colchester  CO4 3SQ , UK

2. Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo , Oslo , Norway

3. Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , London E1 2AT , UK

4. National Heart and Lung Institute, Imperial College London , London SW3 6LY , UK

5. Institute of Medical and Biomedical Education, St George's, University of London , Cranmer Terrace, Tooting SW17 0RE, London

6. Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London , London EC1M 6BQ , UK

Abstract

Abstract Transcription factors (TFs) are proteins that affect gene expression by binding to regulatory regions of DNA in a sequence specific manner. The binding of TFs to DNA is controlled by many factors, including the DNA sequence, concentration of TF, chromatin accessibility and co-factors. Here, we systematically investigated the binding mechanism of hundreds of TFs by analysing ChIP-seq data with our explainable statistical model, ChIPanalyser. This tool uses as inputs the DNA sequence binding motif; the capacity to distinguish between strong and weak binding sites; the concentration of TF; and chromatin accessibility. We found that approximately one third of TFs are predicted to bind the genome in a DNA accessibility independent fashion, which includes TFs that can open the chromatin, their co-factors and TFs with similar motifs. Our model predicted this to be the case when the TF binds to its strongest binding regions in the genome, and only a small number of TFs have the capacity to bind dense chromatin at their weakest binding regions, such as CTCF, USF2 and CEBPB. Our study demonstrated that the binding of hundreds of human and mouse TFs is predicted by ChIPanalyser with high accuracy and showed that many TFs can bind dense chromatin.

Funder

University of Essex

Wellcome Trust

Queen Mary University of London

CRUK

Publisher

Oxford University Press (OUP)

Subject

Genetics

Reference97 articles.

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