Total Binding Affinity Profiles of Regulatory Regions Predict Transcription Factor Binding and Gene Expression in Human Cells

PLoS One. 2015 Nov 24;10(11):e0143627. doi: 10.1371/journal.pone.0143627. eCollection 2015.

Abstract

Transcription factors regulate gene expression by binding regulatory DNA. Understanding the rules governing such binding is an essential step in describing the network of regulatory interactions, and its pathological alterations. We show that describing regulatory regions in terms of their profile of total binding affinities for transcription factors leads to increased predictive power compared to methods based on the identification of discrete binding sites. This applies both to the prediction of transcription factor binding as revealed by ChIP-seq experiments and to the prediction of gene expression through RNA-seq. Further significant improvements in predictive power are obtained when regulatory regions are defined based on chromatin states inferred from histone modification data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Binding Sites / genetics
  • Binding Sites / physiology
  • Chromatin Immunoprecipitation
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Protein Binding / genetics
  • Protein Binding / physiology
  • Regulatory Sequences, Nucleic Acid / genetics
  • Regulatory Sequences, Nucleic Acid / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Transcription Factors

Grants and funding

This work was supported by a grant to PP by the Italian Ministry of University and Research (http://www.istruzione.it/) under the PRIN 2010-2011 call, and by funding to the Graduate School of Biomedical Sciences and Oncology of the University of Turin by the same Italian Ministry of University and Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.