NAR’s Breakthrough Articles present high-impact studies answering long-standing questions in the field of nucleic acids research and/or opening up new areas and mechanistic hypotheses for investigation. These articles are chosen by the Editors on the recommendation of Editorial Board Members and Referees. Articles are accompanied by a brief synopsis explaining the findings of the paper and where they fit in the broader context of nucleic acids research. They represent the very best papers published at NAR.
In this study, the authors describe how epigenetic mechanisms produce cell-to-cell variations of gene expression that may benefit bacterial populations by generating phenotypic diversity. The authors investigated this topic by studying Dam methylase dependent bistable gene regulation in Salmonella. They identified patterns of gene regulation dependent upon several undermethylated Dam sites, confirmed the dependence on DNA adenine methylation and environmental conditions, identified responsible DNA binding proteins, and showed independent switching of different genes.
Promoters serve a critical role in establishing baseline transcriptional capacity through the recruitment of proteins, including transcription factors. Previously, a paucity of data for cis-regulatory elements in plants meant that it was challenging to determine which sequence elements in plant promoter sequences contributed to transcriptional function. In this study, we have identified functional elements in the promoters of plant genes and plant pathogens that utilize plant transcriptional machinery for gene expression. We have established a quantitative experimental system to investigate transcriptional function, investigating how identity, density and position contribute to regulatory function. We then identified permissive architectures for minimal synthetic plant promoters enabling the computational design of a suite of synthetic promoters of different strengths. These have been used to regulate the relative expression of output genes in simple genetic devices.
Brown et al. provide several lines of evidence that acidic intracellular compartments serve as a longterm depot for GalNAc-siRNA conjugates and are the major contributor to the extended duration of activity observed in vivo. Essentially, this serves as a living slow release mechanism that provides compound in the cytosol gradually, thereby enabling long term control of gene expression . This work explains the biological origins of the long duration of effect, and could improve strategies for drug development, clinical trial design, and long-term administration of siRNA drugs to patients.