A pair of newly released papers prove that you don’t always have to run more wet lab experiments to learn something new, you just need to look the data in a different way. The two research groups both used simulations and prediction algorithms, like the ones found on our Epigenetics Databases and Tools list, to pick up new insights into the hard-to-decipher worlds of nucleosome occupancy and miRNA targeting.
Sequence Effects on Nucleosome Position
In the first paper, Dutch scientists from Radboud and Leiden Universities constructed a nucleosome position prediction model. Their algorithm combined the knowledge that nucleosomes prefer certain DNA dinucleotides, with information about free binding energies to get a better picture of how DNA sequence influences nucleosome occupancy.
The model was able to predict nucleosome occupancy with impressive correlation coefficients within both in vitro (0.74) and in vivo (0.66) systems, with the largest deviations in vivo found around transcription start sites.
The authors think their fairly simple algorithm can help in further studies on DNA sequence and chromatin organization. Find out more on nucleosome positions at PNAS, August 2012.
Targeting Rules of miRNA Complexes
The second report comes from the labs of Isidore Rigoutsos (Thomas Jefferson University) and Ruhong Zhou (Columbia University) where they generated simulations in order to study how RISC and miRNA targeting complexes really work. Using their simulations, they tinkered with G:U wobbles, mismatches all across the miRNA ‘seed’ region, and ran all-atom molecular dynamics simulations of Ago-miRNA:mRNA complexes.
The researchers found that many combinations of multiple G:U wobbles and mismatches in the seed region, often aren’t enough to stop target binding, and don’t affect complex stability very much; results that are different from what the current canonical seed-model would have predicted.
The authors suggest that their new insights might explain previous reports of off-target regulation with the use of some siRNAs. Get the new rules of miRNA targeting at Nature Scientific Reports, August 2012.