Science this week features a series of reviews around gene modification. In the first, researchers from Institut Curie discuss new technologies that have enabled the study of chromatin dynamics to better understand their role in the generation of pluripotent stem cells, cell fate decision, and cellular reprogramming. Such insights could help improve the overall understanding of normal development and pathological conditions, with avenues for potential therapeutic application, they write. In a second review, a group of US and UK scientists focus on DNA methylation, which has been shown to play roles in areas such as learning and aging. New single-cell measurement techniques and editing tools, they say, will allow the discovery of "new biological functions (or the debunking of proposed ones) for DNA methylation ... at an unprecedented pace." In a third review, researchers from Princeton University and the European Molecular Biology Laboratory address the interaction of remote gene enhancers with their targets, which they call "one of the central mysteries of genome organization and function." While a variety of contrasting mechanisms have been proposed — including enhancer tracking, linking, looping, and mobilization to transcription factories — they argue that extreme versions of these mechanisms cannot account for the transcriptional dynamics and precision seen in living cells, tissues, and embryos. Emerging evidence instead points to "dynamic three-dimensional hbs that combine different elements of the classical models," they write. In the last review, researchers from the University of Cambridge and the University of Chicago highlight RNA modifications and how they have emerged as "critical posttranscriptional regulators of gene expression programs." New tools and technologies still need to be developed, however, to fully understand how RNA modifications contribute to these processes, particularly at the mechanistic level, they note.
Also in Science, a group led by Max Planck Institute for Evolutionary Anthropology scientists describes the use of Cre-loxP reporter lineage tracking and single-cell RNA sequencing to investigate the cells involved in salamander limb regeneration. By studying the area around the amputated forelimb of a type of salamander called the axolotl, they find periskeletal cells extend existing bone while fibroblasts build new limb segments. Notably, the fibroblast population was found to revert to a skeletal cell progenitor that was responsible for initiating a gene expression program for limb regrowth. "The molecular reprogrammability of adult cells to cells of embryonic limb potential capable of orchestrating complex limb morphogenesis has clear implications for future prospects in regenerative engineering," they conclude. GenomeWeb has more on this, here.