Physical properties of naked DNA influence nucleosome positioning and correlate with transcription start and termination sites in yeast
- Equal contributors
1 Institute for Research in Biomedicine and Barcelona Supercomputing Center Joint Research Program on Computational Biology. Baldiri i Reixac 10. Barcelona 08028. Spain
2 Laufer center for physical and quantitative Biology, Stony Brook University, Stony Brook, NY 11794, USA
3 Department of Biochemistry and Molecular Biology. University of Barcelona. Avinguda Diagonal. Barcelona 08028. Spain
4 Instituto Nacional de Bioinformática. Parc Científic de Barcelona. Baldiri i Reixac 10. Barcelona 08028. Spain
BMC Genomics 2011, 12:489 doi:10.1186/1471-2164-12-489Published: 7 October 2011
In eukaryotic organisms, DNA is packaged into chromatin structure, where most of DNA is wrapped into nucleosomes. DNA compaction and nucleosome positioning have clear functional implications, since they modulate the accessibility of genomic regions to regulatory proteins. Despite the intensive research effort focused in this area, the rules defining nucleosome positioning and the location of DNA regulatory regions still remain elusive.
Naked (histone-free) and nucleosomal DNA from yeast were digested by microccocal nuclease (MNase) and sequenced genome-wide. MNase cutting preferences were determined for both naked and nucleosomal DNAs. Integration of their sequencing profiles with DNA conformational descriptors derived from atomistic molecular dynamic simulations enabled us to extract the physical properties of DNA on a genomic scale and to correlate them with chromatin structure and gene regulation. The local structure of DNA around regulatory regions was found to be unusually flexible and to display a unique pattern of nucleosome positioning. Ab initio physical descriptors derived from molecular dynamics were used to develop a computational method that accurately predicts nucleosome enriched and depleted regions.
Our experimental and computational analyses jointly demonstrate a clear correlation between sequence-dependent physical properties of naked DNA and regulatory signals in the chromatin structure. These results demonstrate that nucleosome positioning around TSS (Transcription Start Site) and TTS (Transcription Termination Site) (at least in yeast) is strongly dependent on DNA physical properties, which can define a basal regulatory mechanism of gene expression.