ArticleACS synthetic biology2023
Tuning Methylation-Dependent Silencing Dynamics by Synthetic Modulation of CpG Density.
Article in ACS synthetic biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
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- MGMT, NUPR1, NDRG2, and GLI1 Gene Promoter Methylation in Glioblastoma Tissues and Association with Clinical Characteristics and Therapeutic Outcomes.International journal of molecular sciences · 2026Article
- Reversing transgene silencing via targeted chromatin editing.bioRxiv : the preprint server for biology · 2025Article
- Unmasking the Epigenome: Insights into Testicular Cell Dynamics and Reproductive Function.International journal of molecular sciences · 2025Review
- Characterization of Rationally Designed CRISPR/Cas9-Based DNA Methyltransferases with Distinct Methyltransferase and Gene Silencing Activities in Human Cell Lines and Primary Human T Cells.ACS synthetic biology · 2025Article
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- High-throughput development and characterization of new functional nanobodies for gene regulation and epigenetic control in human cells.bioRxiv : the preprint server for biology · 2024Article
- Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor.Science (New York, N.Y.) · 2024Article
- Epigenomic insights into common human disease pathology.Cellular and molecular life sciences : CMLS · 2024Review
- The H3.3 K36M oncohistone disrupts the establishment of epigenetic memory through loss of DNA methylation.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Methylation of cytosines in CG dinucleotides (CpGs) within promoters has been shown to lead to gene silencing in mammals in natural contexts. Recently, engineered recruitment of methyltransferases (DNMTs) at specific loci was shown to be sufficient to silence synthetic and endogenous gene expression through this mechanism. A critical parameter for DNA methylation-based silencing is the distribution of CpGs within the target promoter. However, how the number or density of CpGs in the target promoter affects the dynamics of silencing by DNMT recruitment has remained unclear. Here, we constructed a library of promoters with systematically varying CpG content, and analyzed the rate of silencing in response to recruitment of DNMT. We observed a tight correlation between silencing rate and CpG content. Further, methylation-specific analysis revealed a constant accumulation rate of methylation at the promoter after DNMT recruitment. We identified a single CpG site between TATA box and transcription start site (TSS) that accounted for a substantial part of the difference in silencing rates between promoters with differing CpG content, indicating that certain residues play disproportionate roles in controlling silencing. Together, these results provide a library of promoters for synthetic epigenetic and gene regulation applications, as well as insights into the regulatory link between CpG content and silencing rate.
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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.