AI Article Synopsis
- Chemical-induced changes in DNA methylation during fetal development can lead to disorders or increased disease risk later in life.
- The study created a detection assay using human iPS cells with a fluorescent marker to screen for harmful chemicals that affect DNA methylation.
- Analysis of 135 chemicals revealed that those with stronger MBD signals were linked to significant impacts on DNA methylation and gene expression related to cell growth and development, showcasing the assay's potential for advancing drug safety and research.
Article Abstract
Chemical-induced dysregulation of DNA methylation during the fetal period is known to contribute to developmental disorders or increase the risk of certain diseases later in life. In this study, we developed an iGEM (iPS cell-based global epigenetic modulation) detection assay using human induced pluripotent stem (hiPS) cells that express a fluorescently labeled methyl-CpG-binding domain (MBD), which enables a high-throughput screening of epigenetic teratogens/mutagens. 135 chemicals with known cardiotoxicity and carcinogenicity were categorized according to the MBD signal intensity, which reflects the degree of nuclear spatial distribution/concentration of DNA methylation. Further biological characterization through machine-learning analysis that integrated genome-wide DNA methylation, gene expression profiling, and knowledge-based pathway analysis revealed that chemicals with hyperactive MBD signals strongly associated their effects on DNA methylation and expression of genes involved in cell cycle and development. These results demonstrated that our MBD-based integrated analytical system is a powerful framework for detecting epigenetic compounds and providing mechanism insights of pharmaceutical development for sustainable human health.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10125974 | PMC |
| http://dx.doi.org/10.1038/s41598-023-33729-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Frontal lobe intra-axial schwannoma harboring a CHD7::VGLL3 fusion and heterozygous TSC2 p.F1510del mutation in a young child.
Mol Biol Rep
January 2025
Department of Pathology and Laboratory Medicine, Baylor Scott and White Medical Center, Baylor College of Medicine, Temple, TX, USA.
Background: Brain intraparenchymal schwannoma is a rare clinical entity, generally curable with adequate resection.
Methods And Results: We describe a case in a male patient first presenting at 19 months of age, the youngest reported age for this lesion. It also appears to be the first case connected to a germline TSC2 p.
Modeling DNA methyltransferase function to predict epigenetic correlation patterns in healthy and cancer cells.
Proc Natl Acad Sci U S A
January 2025
Department of Chemical Engineering, Stanford University, Stanford, CA 94305.
DNA methylation is a crucial epigenetic modification that orchestrates chromatin remodelers that suppress transcription, and aberrations in DNA methylation result in a variety of conditions such as cancers and developmental disorders. While it is understood that methylation occurs at CpG-rich DNA regions, it is less understood how distinct methylation profiles are established within various cell types. In this work, we develop a molecular-transport model that depicts the genomic exploration of DNA methyltransferase within a multiscale DNA environment, incorporating biologically relevant factors like methylation rate and CpG density to predict how patterns are established.
View Article and Find Full Text PDFTesting the potential of zebularine to induce heritable changes in crop growth and development.
Theor Appl Genet
January 2025
CSIRO Agriculture and Food, Canberra, ACT, 2601, Australia.
Zebularine-treated wheat uncovered a phenotype with characteristics of an epigenetically regulated trait, but major chromosomal aberrations, not DNA methylation changes, are the cause, making zebularine unsuitable for epigenetic breeding. Breeding to identify disease-resistant and climate-tolerant high-yielding wheats has led to yield increases over many years, but new hardy, higher yielding varieties are still needed to improve food security in the face of climate change. Traditional breeding to develop new cultivars of wheat is a lengthy process taking more than seven years from the initial cross to cultivar release.
View Article and Find Full Text PDFSelective adsorption of unmethylated DNA on ZnO nanowires for separation of methylated DNA.
Lab Chip
January 2025
Department of Life Science and Technology, Tokyo Institute of Technology, Nagatsuta 4259, Midori-ku, Yokohama 226-8501, Japan.
DNA methylation is a crucial epigenetic modification used as a biomarker for early cancer progression. However, existing methods for DNA methylation analysis are complex, time-consuming, and prone to DNA degradation. This work demonstrates selective capture of unmethylated DNAs using ZnO nanowires without chemical or biological modifications, thereby concentrating methylated DNA, particularly those with high methylation levels that can predict cancer risk.
View Article and Find Full Text PDFMethylation of foreign DNA overcomes the restriction barrier of and allows efficient genetic manipulation.
Appl Environ Microbiol
January 2025
Department of Biological Sciences, Minnesota State University Mankato, Mankato, Minnesota, USA.
Unlabelled: causes bacterial cold-water disease (BCWD) in salmonids and other fish, resulting in substantial economic losses in aquaculture worldwide. The mechanisms uses to cause disease are poorly understood. Despite considerable effort, most strains of have resisted attempts at genetic manipulation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!