Background: Epigenetic changes occur in response to environmental factors during the pathogenesis of necrotizing enterocolitis (NEC) in animal models, but the DNA methylation signature in human patients with NEC has not been examined.
Aim: To illustrate the signature and function of DNA methylation in the intestine of human NEC.
Methods: DNA methyltransferases (DNMTs) were compared between intestinal tissue with NEC and control. Genome-wide DNA methylation was analyzed by reduced representation bisulfite sequencing (RRBS). The biological functions of the potential methylation regulated genes were analyzed by Gene Ontology. Gene methylation and expression were confirmed by bisulfite genomic sequencing (BGS) and RT-qPCR.
Results: By screening the expression of DNMTs, we identified a marked reduction in DNMT3A at both the mRNA and protein levels in NEC. Genome-wide variation of DNA methylation was detected in NEC lesions. The CG methylation level in almost all unique regions except CpG islands (CGIs) was lower in NEC compared with control. A total of 287 differentially methylated regions (DMRs) were identified across the whole genome in NEC, 123 of them are located on the CGI in the promoter. The DMR-associated genes were linked to intestinal epithelial permeability, platelet aggregation, and lymphocyte proliferation. Four genes (ZNF335, MPL, RASAL3, and KDM6A) with roles in the regulation of lymphocytes that may predispose the intestine to imbalanced immune processes were further confirmed to be hypermethylated and transcriptionally downregulated.
Conclusions: These findings underscore the novel relationship between epigenetic changes and lymphocyte regulation in human NEC, which may have potential diagnostic and therapeutic relevance for NEC.
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http://dx.doi.org/10.1007/s10620-021-07314-6 | DOI Listing |
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.
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 PDFTheor 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 PDFLab 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 PDFAppl 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.
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