Project description:Histologic diagnosis of sellar masses can be challenging, particularly in rare neoplasms and tumors without definitive biomarkers. DNA methylation has recently emerged as a useful diagnostic tool. To illustrate the clinical utility of machine-learning-based DNA methylation classifiers, we report a rare case of primary sellar esthesioneuroblastoma diagnosed by DNA methylation classificiation but histologically mimicking a nonfunctioning pituitary adenoma.
Project description:DNA methylation is a key epigenetic modification regulating genome organization, stability, and gene expression. Stable DNA methylation critically relies on methyl groups provided through folate-mediated one-carbon (C1) metabolism, yet the origin and regulation of C1 supply remain elusive. Here we demonstrate that photorespiration serves as a major C1 source for DNA methylation in Arabidopsis. We show that C1 from formate, a photorespiratory byproduct, is incorporated into 5-methyl-cytosine via the reductive cytosolic folate pathway. This occurs predominantly during the day, negatively regulating serine utilization as alternative C1 source. Consequently, suppression of photorespiration under elevated CO₂ levels alters the DNA methylation landscape, an effect exacerbated when regulation of C1 metabolism by the formate-dependent pathway is impaired. Thus, our findings link the fundamental metabolic process of photorespiration to epigenetic stability, highlighting how rising atmospheric CO₂ levels can induce DNA methylation changes.
Project description:Recently, it has been proposed that local DNA methylation profiles might be dictated by cis-regulatory DNA sequences that mainly operate via DNA-binding factors. Combining blood genome-wide DNA methylation profiles (Illumina Infinium MethylationEPIC BeadChiP), whole genome sequencing-derived single nucleotide variants (SNVs) along with predicted transcription factor binding site (TFBS), we were able to observe that rare regulatory variants, i.e, SNVs that disrupt TFBSs, are associated with DNA methylation at both local and, to a lesser extent, broader locations. Interestingly, we also observed that this directed DNA methylation can have consequences on genome regulation by altering expression levels of nearby genes.