DNA breathing dynamics distinguish binding from nonbinding consensus sites for transcription factor YY1 in cells
Open Access
- 13 August 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 40 (20), 10116-10123
- https://doi.org/10.1093/nar/gks758
Abstract
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.Keywords
This publication has 27 references indexed in Scilit:
- Nucleosome-mediated cooperativity between transcription factorsProceedings of the National Academy of Sciences of the United States of America, 2010
- DNA dynamics play a role as a basal transcription factor in the positioning and regulation of gene transcription initiationNucleic Acids Research, 2009
- Inherited Variation in Gene ExpressionAnnual Review of Genomics and Human Genetics, 2009
- Rapid spontaneous accessibility of nucleosomal DNANature Structural & Molecular Biology, 2004
- The Functions of Plasminogen in Cardiovascular DiseaseTrends in Cardiovascular Medicine, 2004
- Collaborative Competition Mechanism for Gene Activation In VivoMolecular and Cellular Biology, 2003
- TATA-binding protein-independent initiation: YY1, TFIIB, and RNA polymerase II direct basal transcription on supercoiled template DNACell, 1994
- Nonlinear dynamics in a double-chain model of DNAPhysical Review B, 1991
- Statistical mechanics of a nonlinear model for DNA denaturationPhysical Review Letters, 1989
- Phase Transitions in One Dimension and the Helix—Coil Transition in Polyamino AcidsThe Journal of Chemical Physics, 1966