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CRISPR-tools for physiology & cell state changes - potential of transcriptional engineering and epigenome editing.

Physiol. Rev. 101, 177-211 (2021)
Publ. Version/Full Text Postprint DOI
Open Access Green
Given the large amount of genome-wide data that have 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.
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Publication type Article: Journal article
Document type Review
Keywords Cell States ; Cell Types ; Crispr ; Dcas9 ; Epigenetic Screens ; Epigenome Editing ; Transcriptional Engineering; Controlling Gene-expression; Sequence-specific Control; Targeted Dna Methylation; Rna-guided Endonuclease; De-novo Methylation; Beta-globin Gene; Histone Acetylation; Crystal-structure; Endogenous Genes; Chemical Control
ISSN (print) / ISBN 0031-9333
e-ISSN 1522-1210
Quellenangaben Volume: 101, Issue: 1, Pages: 177-211 Article Number: , Supplement: ,
Publisher American Physiological Society
Publishing Place 9650 Rockville Pike, Bethesda, Md 20814 Usa
Reviewing status Peer reviewed
Grants Deutsche Forschungsgemeinschaft