N(6)-methyladenosine (m(6)A) is the most ubiquitous mRNA base modification, but little is known about its precise location, temporal dynamics, and regulation. Here, we generated genomic maps of m(6)A sites in meiotic yeast transcripts at nearly single-nucleotide resolution, identifying 1,308 putatively methylated sites within 1,183 transcripts. We validated eight out of eight methylation sites in different genes with direct genetic analysis, demonstrated that methylated sites are significantly conserved in a related species, and built a model that predicts methylated sites directly from sequence. Sites vary in their methylation profiles along a dense meiotic time course and are regulated both locally, via predictable methylatability of each site, and globally, through the core meiotic circuitry. The methyltransferase complex components localize to the yeast nucleolus, and this localization is essential for mRNA methylation. Our data illuminate a conserved, dynamically regulated methylation program in yeast meiosis and provide an important resource for studying the function of this epitranscriptomic modification.
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http://dx.doi.org/10.1016/j.cell.2013.10.047 | DOI Listing |
Nucleic Acids Res
January 2025
Department of Genetics, The Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Genome graphs, including the recently released draft human pangenome graph, can represent the breadth of genetic diversity and thus transcend the limits of traditional linear reference genomes. However, there are no genome-graph-compatible tools for analyzing whole genome bisulfite sequencing (WGBS) data. To close this gap, we introduce methylGrapher, a tool tailored for accurate DNA methylation analysis by mapping WGBS data to a genome graph.
View Article and Find Full Text PDFBioinform Adv
January 2025
Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, D-69120 Heidelberg, Germany.
Motivation: Since their introduction about 10 years ago, methylation clocks have provided broad insights into the biological age of different species, tissues, and in the context of several diseases or aging. However, their application to single-cell methylation data remains a major challenge, because of the inherent sparsity of such data, as many CpG sites are not covered. A methylation clock applicable on single-cell level could help to further disentangle the processes that drive the ticking of epigenetic clocks.
View Article and Find Full Text PDFDespite considerable advances in identifying risk factors for obesity development, there remains substantial gaps in our knowledge about its etiology. Variation in obesity (defined by BMI) is thought to be due in part to heritable factors; however, obesity-associated genetic variants only account for a small portion of heritability. Epigenetic regulation, defined by genetic and/or environmental factors with changes in gene expression, may account for some of this "missing heritability".
View Article and Find Full Text PDFACS Omega
January 2025
School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, 99 Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani 12120, Thailand.
The integration of molecular docking and AM1 calculations has elucidated the complexation behavior of butylone enantiomers with methylated β-cyclodextrin derivatives. Our study reveals that butylone can adopt two distinct conformations within the β-cyclodextrin cavity, with one conformation being preferentially stabilized due to its favorable binding energy. This conformation preference is influenced by the methylation at the O2, O3, and O6 positions of β-cyclodextrin, which significantly affects complex stability and solvation properties.
View Article and Find Full Text PDFEndocrinology
January 2025
Neuroendocrinology Department, ICMR-National Institute for Research in Reproductive and Child Health, J. M. Street, Parel, Mumbai 400012, India.
Estrogen through its receptors, ERα and ERβ, regulate various aspects of spermatogenesis and male fertility. Since the sperm epigenome is an important contributing factor to male fertility, we evaluated the effects of estrogen signaling activation through the ERs on sperm DNA methylome in adult rats. Whole genome-bisulfite sequencing (WGBS) in caudal sperm DNA was performed.
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