Search

Cas9 DNA targeting is inherently sequence specific but not temporally controlled. Here, authors spatiotemporally couple Cas9 activity to target site transcription in eukaryotes and exploit this to preferentially edit the more highly transcribed of two alleles that harbor identical Cas9 targets.

Multi-omics profiling of the blood and heart of two human decedents receiving pig heart xenografts, including single-cell studies, reveals early immune responses and perioperative cardiac xenograft dysfunction in one of the two decedents, which may be due to mismatched heart size and/or insufficient immunosuppression.

An insertion of an Alu element into an intron of the TBXT gene is identified as a genetic mechanism of tail-loss evolution in humans and apes, with implications for human health today.

Analyses of transcription and chromatin states during the yeast metabolic cycle reveal the links between different chromatin modifications and gene expression. The data also show that chromatin-modifier occupancies do not precisely match modification patterns.

The PAM specificity of SpCas9 can be altered with positive selection during directed evolution. Here the authors use simultaneous positive and negative selection to improve activity on NAG PAMs while reducing activity on NGG PAMs.

Introduction of a long synthetic DNA into yeast genomic loci results in high default transcriptional activity in yeast but low activity in mouse, suggesting distinct default levels of genomic activity in these organisms.

This study describes a method to insert large stretches of exogenous DNA into mammalian genomes, which is used to insert human ACE2 loci into mouse to produce a model of human SARS-CoV-2 infection.

Bikaverin is a fungal-derived tetracyclic polyketide with antibiotic, antifungal and anticancer properties. Here, the authors employ various pathway engineering strategies to achieve high level production of bikaverin in baker’s yeast.

Whole-genome siRNA screens to identify regulators of human LINE-1 retrotransposition reveal that BRCA1 and Fanconi anemia DNA repair factors inhibit retrotransposition at stalled replication fork targets created and exploited by L1.

SCRaMbLE has been used to rearrange synthetic chromosomes that have been introduced into host yeast. Here the authors produce semi-synthetic heterozygous diploid strains for rapid selection of phenotypes and map the rearrangements underlying selected phenotypes such as thermoresistance and caffeine resistance.

In a short-term study in which hearts from gene-edited pigs were transplanted into two recently deceased human recipients, the hearts were able to function for the duration of the study without signs of rejection and without evidence of pig virus transmission, encouraging further clinical study of cardiac xenotransplantation.

The Sc2.0 project involved synthesis and debugging of 16 chromosomes, and a tRNA neochromosome. Here the authors descript the SynXVI project, accompanied by an analysis of how similar projects could operate with hindsight and newly available technologies, and lessons learned from Sc2.0.

The de novo design and synthesis of the Sc 2.0 chromosome XIII enable in-depth investigations into biology. Here the authors construct the 884 Kb synXIII of Saccharomyces cerevisiae to investigate replicative aging.

SCRaMbLE allows for the rapid and large scale rearrangement of genetic data in yeast carrying synthetic chromosomes. Here the authors demonstrate an in vitro use of the method to generate DNA libraries for optimization of biochemical reactions.

In Saccharomyces cerevisiae, the left arm of chromosome XII only requires 12 genes to maintain cell viability, whereas 25 genes are needed for robust fitness. Here the authors demonstrate that the entire arm can be replaced by a neochromosome with completely artificial sequences.

Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) is a promising tool to study genomic rearrangements. Here the authors present an engineered yeast strain with 83 sparsely distributed loxPsym sites across the genome can genrerate large-scale genomic rearrangements, which benefits cell fitness under stress and boosts the SCRaMbLE system when combined with synthetic chromosomes.

Alteration of a stop codon across an entire bacterial genome opens the way to exploring the biotech potential of synthetic genetic codes.

The transcriptional program underlying the origin of glial cells is unclear. Here the authors leverage single-cell/single-nucleus transcriptional and chromatin accessibility profiling to identify candidate cell fate specification genes and optimize a rapid astrocyte differentiation protocol.

The Origin Recognition Complex (ORC) plays conserved and diverse roles in eukaryotes. Here the authors present the structure of a chromatin interacting domain of yeast Orc1 in complex with the nucleosome core particle, revealing that Orc1 interacts with the histone H4 tail irrespective of K16 acetylation; a modification that regulates accessibility to chromatin.

During cellular senescence in human and mouse cells, L1 transposons become transcriptionally derepressed and trigger a type-1 interferon response, which contributes to age-associated inflammation and age-related phenotypes.

Knockout screens to assess the effect of LINE-1 expression on cell growth show that TP53-deficient cells require replication-stress signaling and replication-fork restart factors to suppress LINE-1 toxicity, and that LINE-1 expression activates the Fanconi anemia pathway, suggesting that retrotransposition conflicts with DNA replication.

Yeast chromosomes have been fused to produce viable strains with only two chromosomes that are reproductively isolated from the sixteen-chromosome wild type, but otherwise show high fitness in mitosis and meiosis.

Genetic interaction profiles of human lysine deacetylases are generated by RNA interference knockdown to reveal the involvement of deacetylases in many critical biological processes, including metabolism, the cell cycle and development.

Sensor proteins that exploit principles of linkage-specific avidity reveal topology-related functions of polyubiquitin in diverse cell types and pathways.

The SCRaMbLE system integrated into Sc2.0’s synthetic yeast chromosome project allows rapid strain evolution. Here the authors use a genetic logic gate to control induction of recombination in a haploid and diploid yeast carrying synthetic chromosomes.

A bottleneck to engineered multicellular systems is the lack of a scalable signalling language. Here the authors use fungal mating peptide and GPCR pairs to build functional cell-to-cell communication links.

According to the exon-shuffling hypothesis, new genes are assembled from chunks of old ones. But how? A study of the L1 retrotransposon —which usually moves its own sequence from one genomic location to another —suggests a new mechanism. This retrotransposon can co-mobilize a 3' flanking segment of non-L1 DNA to new locations, allowing the juxtaposition of two previously unlinked DNAs.

Studies of a bacterial virus have revealed an unexpected weapon that helps it to overcome its host's rapidly changing defences. A look at other organisms hints that the mechanism might be widespread.

A collection of 1,406 high-quality, immunoprecipitation- and immunoblotting-grade monoclonal antibodies to 737 human transcription factors is made available as a community resource, along with all validation data.

The authors find that alterations in retrotransposition can occur at different stages in the evolution of pancreatic adenocarcinoma.