Genetic Engineering Publications - GEG Tech top picks

In mammals, parthenogenesis is limited because of problems arising from genomic imprinting. Here, the scientists report live mammalian offspring derived from single unfertilized eggs. This was achieved by the targeted DNA methylation rewriting of seven imprinting control regions. By designing guide RNAs with protospacer adjacent motif (PAM) sequences matching one allele but not the other, dCas9-Dnmt3a or dCpf1-Tet1 enables targeted DNA methylation editing in an allele-specific manner. The success of parthenogenesis in mammals opens many opportunities in agriculture, research, and medicine.

Here the authors describe a Cas9-based histone deacetylase (HDAC) and the design principles required to achieve locus-specific histone deacetylation. They assess its range of activity and specificity, and analyse target gene expression in two different cell types to investigate cellular context-dependent effects. Their findings demonstrate that the chromatin environment is an important element to consider when utilizing this synthetic HDAC.

In this chapter, the authors discuss the current state of epigenomic profiling and how functional information can be indirectly inferred. They also present new approaches that promise definitive functional answers, which are collectively referred to as 'epigenome editing'. In particular, they explore CRISPR-based technologies for single-locus and multi-locus manipulation. Finally, they discuss which level of function can be achieved with each approach and introduce emerging strategies for high-throughput progression from profiles to function.

Large genome-mapping consortia and thousands of genome-wide association studies have identified non-protein-coding elements in the genome as having a central role in various biological processes. However, decoding the functions of the millions of putative regulatory elements discovered in these studies remains challenging. Here the scientists describe CRISPR–Cas9-based epigenomic regulatory element screening (CERES) for improved high-throughput screening of regulatory element activity in the native genomic context. This technology allows the high-throughput functional annotation of putative regulatory elements in their native chromosomal context.