71 Genomic regions flanking E-box binding sites influence DNA binding specificity of bHLH transcription factors through DNA shape

Transcriptional regulation of gene expression is enacted mainly through binding of transcription factors (TFs) to specific, short DNA sites in cis-regulatory regions of genes. Most TFs are members of protein families that share a common DNA-binding domain and thus recognize similar DNA-binding sequences. It is not well understood why paralogous TFs often bind different genomic target sites in vivo to effect different regulatory programs, despite apparently recognizing the same sequence motifs. Here, we designed custom protein-binding microarrays (PBMs) to analyze the DNA-binding specificities of two Saccharomyces cerevisiae basic helix-loop-helix (bHLH) proteins, Tye7 and Cbf1, as a model system. Our data reveal that E-box DNA-binding sequences (CAnnTG), when tested in the context of their native genomic flanking sequences, are bound differently by Cbf1 and Tye7. Computational models of the PBM data indicate that DNA sequence features located in the genomic sequences outside the E-box contribute to DNA-bi...