ArticleACS synthetic biology2018
Targeted Gene Repression Using Novel Bifunctional Molecules to Harness Endogenous Histone Deacetylation Activity.
Article in ACS synthetic biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
17 citing papers in PubMed, 27 citations in OpenAlex.
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 2026Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- A First-in-Class Chemical-Induced Proximity System Achieves Dose-Dependent Control of Tumor Protein P53 Gene Activation in Preclinical Models of Gastric Cancer.ACS pharmacology & translational science · 2025Article
- Development of artificial transcription factors and their applications in cell reprograming, genetic screen, and disease treatment.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Engineered Cas9 variants bypass Keap1-mediated degradation in human cells and enhance epigenome editing efficiency.Nucleic acids research · 2024Article
- Induced proximity labeling and editing for epigenetic research.Cell chemical biology · 2024Review
- Context-specific functions of chromatin remodellers in development and disease.Nature reviews. Genetics · 2024Review
- Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Chemical Epigenetic Regulation of Adeno-Associated Virus Delivered Transgenes.Human gene therapy · 2023Article
- Bioorthogonal Chemical Epigenetic Modifiers Enable Dose-Dependent CRISPR Targeted Gene Activation in Mammalian Cells.ACS synthetic biology · 2022Article
- Getting a handle on chemical probes of chomatin readers.Future medicinal chemistry · 2021Article
- Chemical and Light Inducible Epigenome Editing.International journal of molecular sciences · 2020Review
- Epigenetic Control of a Local Chromatin Landscape.International journal of molecular sciences · 2020Review
- Contribution of promoter DNA sequence to heterochromatin formation velocity and memory of gene repression in mouse embryo fibroblasts.PloS one · 2019Article
- Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers.Journal of visualized experiments : JoVE · 2018Article
- Cavitation Enhancement Increases the Efficiency and Consistency of Chromatin Fragmentation from Fixed Cells for Downstream Quantitative Applications.Biochemistry · 2018Article
- FKBP Ligands-Where We Are and Where to Go?Frontiers in pharmacology · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Epigenome editing is a powerful method for life science research and could give rise to new therapies for diseases initiated or maintained by epigenetic dysregulation, including several types of cancers and autoimmune disorders. In addition, much is still unknown about the mechanisms by which histone-modifying proteins work in concert to properly regulate gene expression. To investigate and manipulate complex epigenetic interactions in live cells, we have developed a small molecule platform for specifically inducing gene repression and histone deacetylation at a reporter gene. We synthesized bifunctional ligands, or chemical epigenetic modifiers (CEMs), that contain two functional groups: a FK506 derivative capable of binding to a FKBP-Gal4 fusion transcription factor, and a histone deacetylase (HDAC) inhibitor that recruits HDAC-containing corepressor complexes. In our reporter cell line, which contains a GFP reporter allele upstream of a Gal4 DNA binding array in the murine Oct4 locus, our lead CEM repressed GFP expression by 50%. We also show that CEM recruitment of deacetylation activity causes marked deacetylation along our target loci. This system allowed us to detail the direct results of deacetylation to chromatin and measure the resulting gene expression in a chemically dependent and reversible manner. The CEMs system provides new insights into epigenetic gene regulation and has the potential to control disease-relevant gene regulation. The CEMs are derived from FDA-approved epigenetic modulator drugs, and use their pharmacology in a gene-specific way that avoids the toxicities and off-target effects caused by whole-cell application of these drugs.
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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.