Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many polymerase chain reaction (PCR)-based methods for diagnosis of minute mutations are suboptimal for automated screening because of their reliance on gel electrophoresis or probe hybridization. In the method reported here, PCR products containing artificial methylation sites are analyzed by measuring incorporation of radiolabeled methyl groups. Primers are designed to amplify the possible mutation-containing region such that the 3' end of one primer lies adjacent to the possible mutation. Sequence modification near that end creates either a mutation- or wild type (WT)-specific artificial methylation site in the PCR product. The product is briefly incubated with an appropriate DNA methylase and tritiated S-adenosylmethionine ([3H]SAM), separated from free SAM by column chromatography, and analyzed for incorporation of tritium. Applying this technique to the cystic fibrosis delta F508 deletion, we accurately diagnosed five homozygotes, five heterozygotes, and five normal individuals within 40 min of PCR completion. The method can be generalized to rapid, automated detection of a variety of point mutations and small deletions.
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PMID:DNA diagnosis with mutation-specific artificial methylation sites: application to rapid screening of delta F508. 145 78

The impaired mucociliary clearance in individuals with Cystic Fibrosis (CF) enables opportunistic pathogens to colonize CF lungs. Here we show that Rothia mucilaginosa is a common CF opportunist that was present in 83% of our patient cohort, almost as prevalent as Pseudomonas aeruginosa (89%). Sequencing of lung microbial metagenomes identified unique R. mucilaginosa strains in each patient, presumably due to evolution within the lung. The de novo assembly of a near-complete R. mucilaginosa (CF1E) genome illuminated a number of potential physiological adaptations to the CF lung, including antibiotic resistance, utilization of extracellular lactate, and modification of the type I restriction-modification system. Metabolic characteristics predicted from the metagenomes suggested R. mucilaginosa have adapted to live within the microaerophilic surface of the mucus layer in CF lungs. The results also highlight the remarkable evolutionary and ecological similarities of many CF pathogens; further examination of these similarities has the potential to guide patient care and treatment.
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PMID:Mechanistic model of Rothia mucilaginosa adaptation toward persistence in the CF lung, based on a genome reconstructed from metagenomic data. 2373 77

Cystic fibrosis (CF) is a deadly genetic disease that affects the lungs and digestive system. A mutation in the CF transmembrane conductance regulator (CFTR) gene is the cause of the disease. How epigenetics contributes to CFTR expression is still poorly understood. Epigenetics is a mechanism that alters gene expression without changing the underlying DNA sequence. Epigenetic mechanisms include DNA methylation and histone modification. Both mechanisms have been implicated in CFTR gene regulation. Here we review epigenetic regulation of CFTR transcription while discussing potential epigenetic targeting strategies including DNA methyltransferase, histone deacetylase, and histone methyltransferase and demethylase inhibition. Because of the reversibility of epigenetics, targeting epigenetic mechanisms has been an attractive therapeutic approach. However, epigenetic targeting of CF disease is still at its infant stage.
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PMID:Epigenetics in Cystic Fibrosis: Epigenetic Targeting of a Genetic Disease. 2588 15