ArticleThe Journal of biological chemistry2018
Small molecules capable of activating DNA methylation-repressed genes targeted by the p38 mitogen-activated protein kinase pathway.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Review
- Pramel15 facilitates zygotic nuclear DNMT1 degradation and DNA demethylation.Nature communications · 2024Article
- Prognostic biomarker GSTK1 in head and neck squamous cell carcinoma and its correlation with immune infiltration and DNA methylation.Frontiers in genetics · 2023Article
- Article
- In Barrett's epithelial cells, weakly acidic bile salt solutions cause oxidative DNA damage with response and repair mediated by p38.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Cardiac Fibroblast p38 MAPK: A Critical Regulator of Myocardial Remodeling.Journal of cardiovascular development and disease · 2019Review
- Stella protein facilitates DNA demethylation by disrupting the chromatin association of the RING finger-type E3 ubiquitin ligase UHRF1.The Journal of biological chemistry · 2019Article
- The proinflammatory cytokine TNFα induces DNA demethylation-dependent and -independent activation ofThe Journal of biological chemistry · 2019Article
- Synthesis and Evaluation of a New Type of Small Molecule Epigenetic Modulator Containing Imidazo[1,2-Frontiers in chemistry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulation of gene expression by epigenetic modifications such as DNA methylation is crucial for developmental and disease processes, including cell differentiation and cancer development. Genes repressed by DNA methylation can be derepressed by various compounds that target DNA methyltransferases, histone deacetylases, and other regulatory factors. However, some additional, unknown mechanisms that promote DNA methylation-mediated gene silencing may exist. Chemical agents that can counteract the effects of epigenetic repression that is not regulated by DNA methyltransferases or histone deacetylases therefore may be of research interest. Here, we report the results of a high-throughput screen using a 308,251-member chemical library to identify potent small molecules that derepress an EGFP reporter gene silenced by DNA methylation. Seven hit compounds were identified that did not directly target bulk DNA methylation or histone acetylation. Analyzing the effect of these compounds on endogenous gene expression, we discovered that three of these compounds (compounds LX-3, LX-4, and LX-5) selectively activate the p38 mitogen-activated protein kinase (MAPK) pathway and derepress a subset of endogenous genes repressed by DNA methylation. Selective agonists of the p38 pathway have been lacking, and our study now provides critical compounds for studying this pathway and p38 MAPK-targeted genes repressed by DNA methylation.
Indexed as
Identifiers
What OpenQuestion holds
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.