  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.
