A new analytical method for simulating high-throughput chromatin conformation (Hi-C) data from interacting genome fragments is presented in Nature Methods this week. Called FreeHi-C — short for fragment interactions empirical estimation for fast simulation of Hi-C data — the approach nonparametrically simulates realistic read-level Hi-C data by emulating the standard Hi-C experimental protocol, its developers write. Data from FreeHi-C show high fidelity to biological Hi-C data, and the method "boosts the precision and power of differential chromatin interaction detection through data augmentation under preserved false discovery rate control."
Small molecules designed to modify chromatin can be used for the dose-dependent activation of gene expression in combination with CRISPR-Cas9, according to a new report in Nature Biotechnology. The molecules, called chemical epigenetic modifiers (CEMs), activate the expression of target genes by recruiting components of the endogenous chromatin-activating machinery. To achieve targeted gene activation, the study's authors used catalytically inactive Cas9 complexed to FK506-binding protein and a CEM consisting of FK506 linked to a molecule that interacts with cellular epigenetic machinery. They state that these CEMs upregulate gene expression at target endogenous loci up to 20-fold or more depending on the gene in a dose-dependent manner, making the platform "useful in target validation work for visualization of trends between phenotype and gene dosage over a wide range of target gene concentrations."