ArticleThe Journal of biological chemistry2011
Synthetic reversal of epigenetic silencing.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- Reader-Effectors as Actuators of Epigenome Editing.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Design and mathematical analysis of activating transcriptional amplifiers that enable modular temporal control in synthetic juxtacrine circuits.Synthetic and systems biotechnology · 2023Article
- Live-cell imaging unveils distinct R-loop populations with heterogeneous dynamics.Nucleic acids research · 2023Article
- Plant synthetic epigenomic engineering for crop improvement.Science China. Life sciences · 2022Review
- Beyond the marks: reader-effectors as drivers of epigenetics and chromatin engineering.Trends in biochemical sciences · 2022Review
- Chemical Genetic Validation of CSNK2 Substrates Using an Inhibitor-Resistant Mutant in Combination with Triple SILAC Quantitative Phosphoproteomics.Frontiers in molecular biosciences · 2022Article
- Development of a potent and selective chemical probe for the pleiotropic kinase CK2.Cell chemical biology · 2021Article
- Optogenetic control of mRNA localization and translation in live cells.Nature cell biology · 2020Article
- Programmable mutually exclusive alternative splicing for generating RNA and protein diversity.Nature communications · 2019Article
- Article
- The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells.BMC systems biology · 2018Article
- Design, Construction, and Validation of Histone-Binding Effectors in Vitro and in Cells.Biochemistry · 2018Article
- Tandem Histone-Binding Domains Enhance the Activity of a Synthetic Chromatin Effector.ACS synthetic biology · 2018Article
- Molecular structures guide the engineering of chromatin.Nucleic acids research · 2017Article
- The Impact of Chromatin Dynamics on Cas9-Mediated Genome Editing in Human Cells.ACS synthetic biology · 2017Article
- Mammalian synthetic biology for studying the cell.The Journal of cell biology · 2017Review
- Regulation of cancer epigenomes with a histone-binding synthetic transcription factor.NPJ genomic medicine · 2017Article
- The epigenome: the next substrate for engineering.Genome biology · 2016Review
- Unraveling the 3D genome: genomics tools for multiscale exploration.Trends in genetics : TIG · 2015Review
- Enhanced MyoD-induced transdifferentiation to a myogenic lineage by fusion to a potent transactivation domain.ACS synthetic biology · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Controlling cell fate-determining gene expression is key to stem cell differentiation, tissue regeneration, and cancer therapy. To date, custom-built transcription factors recognize the information encoded in specific DNA sequences. Chromatin proteins undergo covalent modifications and form complexes that encode a second layer of information that determines proximal gene activity. Here, we employ a novel gene-targeting approach that exploits a specific chromatin modification to reactivate silenced loci in human cells. We used the human Polycomb chromatin protein and homologues from other species to construct modular synthetic transcription factors, called Pc-TFs, that recognize the repressive trimethyl-histone H3 lysine 27 (H3K27me3) signal and switch silenced genes to an active state. Pc-TF expression in U2OS osteosarcoma cells leads to increased transcription of the senescence locus CDKN2A (p16) and other loci in a chromodomain- and activation module-dependent manner, a switch to a senescence phenotype, and reduced cell proliferation. These results indicate that silenced developmental regulators can be reactivated by a synthetic transcription factor that interacts with chromatin rather than DNA, resulting in an altered cell state. As such, our work extends the flexibility of transcription factor engineering and is the first example of chromatin-mediated synthetic transcription factor targeting.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.