DNA breathing dynamics distinguish binding from nonbinding consensus sites for transcription factor YY1 in cells.
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.
Harvard Medical School, Department of Medicine, Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Boian S
BS
Alexandrov
Yayoi
Y
Fukuyo
Martin
M
Lange
Nobuo
N
Horikoshi
Vladimir
V
Gelev
Kim Ø
KØ
Rasmussen
Alan R
AR
Bishop
Anny
A
Usheva
D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D004247:DNA / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D056004:Molecular Dynamics Simulation; D010958:Plasminogen / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050986:YY1 Transcription Factor / Q000378:metabolism*
D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D010958:Plasminogen; D004247:DNA