CRISPR-tools for physiology & cell state changes - potential of transcriptional engineering and epigenome editing
Christopher T. Breunig, Anna Köferle, Andrea M. Neuner, Maximilian F. Wiesbeck, Valentin Baumann, Stefan H. Stricker
Physiological Reviews 11 Jun 2020 doi.org/10.1152/physrev.00034.2019
Abstract cited from publication:
Given the large amount of genome-wide data that has been collected during the last decades a good understanding of how and why cells change during development, homeostasis and disease might be expected. Unfortunately, the opposite is true; Triggers that cause cellular state changes remain elusive and the underlying molecular mechanisms are poorly understood. Although genes with the potential to influence cell states are known, the historic dependency on methods that manipulate gene expression outside the endogenous chromatin context has prevented us from understanding how cells organize, interpret and protect cellular programs. Fortunately, recent methodological innovations are now providing options to answer these outstanding questions, by allowing to target and manipulate individual genomic and epigenomic loci. In particular, three experimental approaches are now feasible due to DNA targeting tools: namely, activation and/or repression of master transcription factors in their endogenous chromatin context, targeting transcription factors to endogenous, alternative or inaccessible sites; and finally, functional manipulation of the chromatin context. In this article, we discuss the molecular basis of DNA targeting tools and review the potential of these new technologies before we summarize how these have already been used for the manipulation of cellular states and hypothesize about future applications.