Synthetic transcription factors switch from local to long-range control during cell differentiation

Wada, Takeo and Wallerich, Sandrine and Becskei, Attila. (2019) Synthetic transcription factors switch from local to long-range control during cell differentiation. ACS Synthetic Biology, 8 (2). pp. 223-231.

Full text not available from this repository.

Official URL: https://edoc.unibas.ch/68201/

Downloads: Statistics Overview


Genes, including promoters and enhancers, are regulated by short- and long-range interactions in higher eukaryotes. It is unclear how mammalian gene expression subject to such a combinatorial regulation can be controlled by synthetic transcription factors (TF). Here, we studied how synthetic TALE transcriptional activators and repressors affect the expression of genes in a gene array during cellular differentiation. The protocadherin gene array is silent in mouse embryonic stem (ES) and neuronal progenitor cells. The TALE transcriptional activator recruited to a promoter activates specifically the target gene in ES cells. Upon differentiation into neuronal progenitors, the transcriptional regulatory logic changes: the same activator behaves like an enhancer, activating distant genes in a correlated, stochastic fashion. The long-range effect is reflected by the alterations in CpG methylation. Our findings reveal the limits of precision and the opportunities in the control of gene expression for TF-based therapies in cells of various differentiation stages.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Synthetic Microbiology (Becskei)
UniBasel Contributors:Becskei, Attila and Wada, Takeo and Wallerich, Sandrine
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:03 Aug 2020 15:18
Deposited On:03 Aug 2020 15:18

Repository Staff Only: item control page