Physical Properties in naked DNA
Physical Properties of Naked DNA Signal Gene Regulatory Regions
Nucleosome positioning strongly affects gene expression, although the DNA regulatory mechanisms remain elusive. Integration of genome-wide sequencing of micrococcal nuclease-digested yeast naked (histone-free) and nucleosomal DNA with physical descriptors derived from molecular dynamics has enabled us to trace DNA physical properties on a genomic scale. We observed that crucial regulatory regions like transcription start and termination sites are signaled by unusual physical properties of naked DNA. Remarkably, micrococcal nuclease degraded regions in naked and nucleosomal DNA correlate extremely well, suggesting that nucleosome positioning is strongly dependent on physical properties of naked DNA. Indeed, ab initio physical descriptors are able to accurately predict nucleosome enriched and depleted regions. Our analyses thus confirm that DNA physical properties modulate gene expression by influencing nucleosome positioning in key regulatory regions. Overall, our results highlight a previously ignored and probably quite universal mechanism of gene regulation based on fundamental physical properties of the DNA.
In eukaryotic organisms, DNA is packaged into chromatin structure, where most of DNA is wrapped into nucleosomes. Therefore, 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 the issue, the rules defining nucleosome positioning and the location of DNA regulatory regions still remain elusive. Here, we have analyzed the physical properties of yeast DNA by a combination of genome-wide nuclease digestion measurements (of both nucleosomal and naked DNA) with molecular dynamics simulations of short DNA fragments