ArticleBMC systems biology2018
The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells.
Article in BMC systems biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Insulin-like growth factor 1 receptor regulates breast cancer cell adhesion through beta-1 integrin.Frontiers in endocrinology · 2026Article
- Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Synthetic Reader-Actuators Targeted to Polycomb-Silenced Genes Block Triple-Negative Breast Cancer Proliferation and Invasion.GEN biotechnology · 2023Article
- Rapid Single-Pot Assembly of Modular Chromatin Proteins for Epigenetic Engineering.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Beyond the marks: reader-effectors as drivers of epigenetics and chromatin engineering.Trends in biochemical sciences · 2022Review
- Control of mammalian cell-based devices with genetic programming.Current opinion in systems biology · 2021Article
- Histone 3 Lysine 27 Trimethylation Signature in Breast Cancer.International journal of molecular sciences · 2021Review
- Chromatin engineering offers an opportunity to advance epigenetic cancer therapy.Nature structural & molecular biology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMounting evidence from genome-wide studies of cancer shows that chromatin-mediated epigenetic silencing at large cohorts of genes is strongly linked to a poor prognosis. This mechanism is thought to prevent cell differentiation and enable evasion of the immune system. Drugging the cancer epigenome with small molecule inhibitors to release silenced genes from the repressed state has emerged as a powerful approach for cancer research and drug development. Targets of these inhibitors include chromatin-modifying enzymes that can acquire drug-resistant mutations. In order to directly target a generally conserved feature, elevated trimethyl-lysine 27 on histone H3 (H3K27me3), we developed the Polycomb-based Transcription Factor (PcTF), a fusion activator that targets methyl-histone marks via its N-terminal H3K27me3-binding motif, and co-regulates sets of silenced genes.
resultsHere, we report transcriptome profiling analyses of PcTF-treated breast cancer model cell lines. We identified a set of 19 PcTF-upregulated genes, or PUGs, that were consistent across three distinct breast cancer cell lines. These genes are associated with the interferon response pathway.
conclusionsOur results demonstrate for the first time a chromatin-mediated interferon-related transcriptional response driven by an engineered fusion protein that physically links repressive histone marks with active transcription.
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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.