Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex

TL;DR: Results show off-target activity can severely limit identification of essential functional motifs by active Cas9, while strictly filtered CRISPRi screens can be reliably used for assaying larger regulatory elements.

TL;DR: The use of MYB is demonstrated in the context of the CRISPR-activation system, showing that DNA elements and fusion proteins derived from c-myb can mitigate epigenetic silencing to improve transgene expression in engineered cell lines.

TL;DR: This work directly observed dynamic fluctuations of multiple Cas9 domains, using single-molecule FRET, and revealed the conformational flexibility of apo-Cas9, which may play a role in the assembly with the sgRNA.

TL;DR: The recent development of methods to directly screen oncogenic pathways in high-throughput to more directly and efficiently connect functional genomic screening results with therapeutic targets is described.

TL;DR: It is shown that accurate gene-level abundance estimates are best obtained with large numbers of short single-end reads, and estimates of the relative frequencies of isoforms within single genes may be improved through the use of paired- end reads, depending on the number of possible splice forms for each gene.

TL;DR: This study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.

TL;DR: The results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents and the generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of ‘personalized’ therapeutic regimens.

TL;DR: A new version of the database, MSigDB 3.0, is reported, with over 6700 gene sets, a complete revision of the collection of canonical pathways and experimental signatures from publications, enhanced annotations and upgrades to the web site.