transcriptional engineering
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Epigenomes ◽  
2021 ◽  
Vol 5 (3) ◽  
pp. 17
Author(s):  
Annick Dubois ◽  
François Roudier

CRISPR-based epigenome editing uses dCas9 as a platform to recruit transcription or chromatin regulators at chosen loci. Despite recent and ongoing advances, the full potential of these approaches to studying chromatin functions in vivo remains challenging to exploit. In this review we discuss how recent progress in plants and animals provides new routes to investigate the function of chromatin regulators and address the complexity of associated regulations that are often interconnected. While efficient transcriptional engineering methodologies have been developed and can be used as tools to alter the chromatin state of a locus, examples of direct manipulation of chromatin regulators remain scarce in plants. These reports also reveal pitfalls and limitations of epigenome engineering approaches that are nevertheless informative as they are often associated with locus- and context-dependent features, which include DNA accessibility, initial chromatin and transcriptional state or cellular dynamics. Strategies implemented in different organisms to overcome and even take advantage of these limitations are highlighted, which will further improve our ability to establish the causality and hierarchy of chromatin dynamics on genome regulation.


2021 ◽  
Vol 101 (1) ◽  
pp. 177-211
Author(s):  
Christopher T. Breunig ◽  
Anna Köferle ◽  
Andrea M. Neuner ◽  
Maximilian F. Wiesbeck ◽  
Valentin Baumann ◽  
...  

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.


Author(s):  
Srinivasan Balamurugan ◽  
Da-Wei Li ◽  
Xiang Wang ◽  
Wei-Dong Yang ◽  
Jie-Sheng Liu ◽  
...  

2017 ◽  
Vol 35 (3) ◽  
pp. 390-405 ◽  
Author(s):  
Rajesh Mehrotra ◽  
Kaushik Renganaath ◽  
Harsh Kanodia ◽  
Gary J Loake ◽  
Sandhya Mehrotra

2017 ◽  
Vol 35 (2) ◽  
pp. 95-99 ◽  
Author(s):  
Amit K. Bajhaiya ◽  
Javiera Ziehe Moreira ◽  
Jon K. Pittman

2014 ◽  
Vol 9 (6) ◽  
pp. e28736 ◽  
Author(s):  
Wenjia Xu ◽  
Loïc Lepiniec ◽  
Christian Dubos

2013 ◽  
Vol 29 (5) ◽  
pp. 1140-1149 ◽  
Author(s):  
Qiulin Wu ◽  
Aihua Yang ◽  
Wei Zou ◽  
Zuoying Duan ◽  
Jie Liu ◽  
...  

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