DNA sequence correlations shape nonspecific transcription factor-DNA binding affinity

Abstract

Transcription factors (TFs) are regulatory proteins that bind DNA in promoter regions of the genome and either promote or repress gene expression. Here we predict analytically that enhanced homo-oligonucleotide sequence correlations, such as poly(dA:dT) and poly(dC:dG) tracts, statistically enhance non-specific TF-DNA binding affinity. This prediction is generic and qualitatively independent of microscopic parameters of the model. We show that non-specific TF binding affinity is universally controlled by the strength and symmetry of DNA sequence correlations. We perform correlation analysis of the yeast genome and show that DNA regions highly occupied by TFs exhibit stronger homo-oligonucleotide sequence correlations, and thus higher propensity for non-specific binding, as compared with poorly occupied regions. We suggest that this effect plays the role of an effective localization potential enhancing the quasi-one-dimensional diffusion of TFs in the vicinity of DNA, speeding up the stochastic search process for specific TF binding sites. The predicted effect also imposes an upper bound on the size of TF-DNA binding motifs.

References in corpus (5)

• Kinetics of protein-DNA interaction: facilitated target location in sequence-dependent potential
• Nucleosome-mediated cooperativity between transcription factors
• How do proteins search for their specific sites on coiled or globular DNA
• The long reach of DNA sequence heterogeneity in diffusive processes
• Effects of intersegmental transfers on target location by proteins

Cited by in corpus (7)

• Nonspecific transcription factor-DNA binding influences nucleosome occupancy in yeast
• Genome-wide organization of eukaryotic pre-initiation complex is influenced by nonconsensus protein-DNA binding
• Nonspecific Protein-DNA Binding Is Widespread in the Yeast Genome
• Sequence correlations shape protein promiscuity
• Specificity-determining DNA triplet code for positioning of human pre-initiation complex
• Energy fluctuations shape free energy of nonspecific biomolecular interactions
• Discovery and information-theoretic characterization of transcription factor binding sites that act cooperatively