Structure-based identification of new high-affinity nucleosome binding sequences.
|Title||Structure-based identification of new high-affinity nucleosome binding sequences.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Battistini, Federica, Hunter Christopher A., Moore Irene K., and Widom Jonathan|
|Journal||J Mol Biol|
|Date Published||2012 Jun 29|
|Keywords||Base Sequence, Binding Sites, Computational Biology, Computer Simulation, DNA, Histones, Humans, Molecular Sequence Data, Nucleic Acid Conformation, Nucleosomes, Protein Binding|
The substrate for the proteins that express genetic information in the cell is not naked DNA but an assembly of nucleosomes, where the DNA is wrapped around histone proteins. The organization of these nucleosomes on genomic DNA is influenced by the DNA sequence. Here, we present a structure-based computational approach that translates sequence information into the energy required to bend DNA into a nucleosome-bound conformation. The calculations establish the relationship between DNA sequence and histone octamer binding affinity. In silico selection using this model identified several new DNA sequences, which were experimentally found to have histone octamer affinities comparable to the highest-affinity sequences known. The results provide insights into the molecular mechanism through which DNA sequence information encodes its organization. A quantitative appreciation of the thermodynamics of nucleosome positioning and rearrangement will be one of the key factors in understanding the regulation of transcription and in the design of new promoter architectures for the purposes of tuning gene expression dynamics.