DNA breathing dynamics distinguish binding from nonbinding consensus sites for transcription factor YY1 in cells

作者：Boian S. Alexandrov, Yayoi Fukuyo, Martin Lange, Nubuo Horikoshi, Vladimir Gelev, K. Ø. Rasmussen, A. R. Bishop, Anny Usheva · 发表于：Nucleic Acids Research · 年份：2012 · DOI：10.1093/nar/gks758 · 被引用次数：50 · 研究领域：Genomics and Chromatin Dynamics、RNA and protein synthesis mechanisms、RNA Research and Splicing

The genome-wide mapping of the major gene expression regulators, the transcription factors (TFs) and their DNA binding sites, is of great importance for describing cellular behavior and phenotypic diversity. Presently, the methods for prediction of genomic TF binding produce a large number of false positives, most likely due to insufficient description of the physiochemical mechanisms of protein-DNA binding. Growing evidence suggests that, in the cell, the double-stranded DNA (dsDNA) is subject to local transient strands separations (breathing) that contribute to genomic functions. By using site-specific chromatin immunopecipitations, gel shifts, BIOBASE data, and our model that accurately describes the melting behavior and breathing dynamics of dsDNA we report a specific DNA breathing profile found at YY1 binding sites in cells. We find that the genomic flanking sequence variations and SNPs, may exert long-range effects on DNA dynamics and predetermine YY1 binding. The ubiquitous TF YY1 has a fundamental role in essential biological processes by activating, initiating or repressing transcription depending upon the sequence context it binds. We anticipate that consensus binding sequences together with the related DNA dynamics profile may significantly improve the accuracy of genomic TF binding sites and TF binding-related functional SNPs.