Nucleosomes contain 147 bp stretches of DNA, packed into histone octamers. It has been observed that DNA sequences differ in their ability to bend with and bind to the histone octamer, suggesting a sequence preference for nucleosome formation; this sequence constraint may, for example, limit the access to the transcription machinery, thus functioning as a system for gene expression regulation. Two models have been proposed to explain this sequence preference: trans- positional regulation of nucleosome positioning (by nucleosome remodelling complexes); and a cis- regulation model, that expects that the genome encodes sequences with high and low nucleosome affinities. In this paper, Segal et al. used both experimental and computational approaches to show that ~50% of the in vivo nucleosome organization in the yeast genome is explained by the cis- regulation model: First, they employed a genome- wide assay to isolate the DNA forming stably nucleosomes, and then with the resulting sequences, they built a stochastic model containing the information that describes the relative affinities of nucleosomes to bind to specific sequences; this approach was similar to that used in bioinformatics to describe transcription factor binding motifs and patterns. As expected, they found periodicity that resembles the DNA helical repeat, and the same results were obtained with avian sequences, which implied that these genomic positioning signals were strong and perhaps evolutionary conserved. They used several analyses to confirm that positioning was dictated by sequences, and between chromosomal regions, the highest occupancy was over centromeres, and as expected rDNA and tRNA genes presented a notorious low predicted occupancy. Other important sites with low predicted nucleosome occupancy were functional binding sites (46 transcription factor recognition sequences evaluated), and transcription start sites. However, we should keep in mind that these results are just predictions, as the authors also recognize, and they mentioned some improvements that should be taken into account in the future to better determine the nucleosome occupancy, like competition between nucleosome proteins and other DNA binding proteins (that depends on affinity and concentration), consideration of favourable nucleosome interaction thermodynamics, and of course more in vitro experimentation in these and other species. This work could be the first step towards another form of biological information: One that specifies that the nucleosome organization is encoded in the genome.
Segal E. et al. 2006. Nature 442:772-778
epigenetics
An online computational tool was built by the authors, based on the model reported on this paper, that can be found here. More comments can be found in the same issue of Nature1, 2, and at the Faculty of 1000 and EurekAlert websites.
Segal E. et al. 2006. Nature 442:772-778
epigeneticsAn online computational tool was built by the authors, based on the model reported on this paper, that can be found here. More comments can be found in the same issue of Nature1, 2, and at the Faculty of 1000 and EurekAlert websites.
