Analysis of HT-SELEX data implicates the role of DNA shape readout in non-specific binding of Transcription Factors

Authors

• S Pal
• T Przytycka

Abstract

Characterizing the DNA binding specificities of transcription factors is one of the main steps in studying many biological phenomena such as gene expression regulation. High-throughput experimental methods such as HT-SELEX have recently been extensively used to study the specificity of TF-DNA binding in vitro setting. Though, several models and algorithms have been developed to measure the specificities using position weight matrix (PWM) computed from the relative abundance of sequence-motifs in the DNA sequences across SELEX rounds, these PWMs have higher information content due to presence of significantly high non-specific binding to the sequence motifs. Recently, DNA shape readout has been shown to play a significant role in TF-DNA binding. However, to what extent the shape readout affect the binding, particularly the non-specific ones, is not known. We address this problem by a comparative study of the enrichment of the shape readout of subsequences in the two subgroups of the bound DNA sequences: 1) motifers: those containing the core sequence motifs, 2) non-motifers: those containing neither the core sequence motif nor its short distance neighbors. We found that the highly enriched shape-mers in motifers are also enriched in non-motifers. This gives the evidence of shape readout in nonspecific binding. However, we do not see highly enriched shape-mers in non-motifers getting enriched in motifers. We are currently investigating the reason, which we suspect to be the bias of the experimental setup.

Scientific Focus Area: Computational Biology

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