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PubMed2026

Di-, tri-, and tetranucleotide frequencies covary with lifespan and genome size across protostome invertebrates.

Animal lifespans span orders of magnitude, yet how genome sequence covaries with lifespan remains poorly characterized outside vertebrates. Although promoter CpG density has been linked to vertebrate longevity due to its gene-regulatory function through DNA methylation, it is unclear whether such patterns are promoter- and CpG-specific, or if they reflect broader sequence evolution. We curated maximum lifespan estimates for 466 protostome species spanning eight phyla with available genome assemblies and quantified mono-, di-, tri-, and tetranucleotide composition across whole genomes, intergenic regions, and six gene-associated regions (two upstream regions, exons, introns, and two downstream regions) defined using Benchmarking Universal Single-Copy Orthologs. Dinucleotide observed/expected ratios showed significant associations with lifespan and genome size in different ways. Lifespan-associated motifs were most pronounced in gene-associated non-coding regions, especially in introns and downstream regions, whereas genome-size effects were strongest in whole-genome and intergenic sequence. Tri- and tetranucleotide observed/expected ratios broadly recapitulated this regional organization. In contrast, GC content was not associated with lifespan across regions, indicating that the observed signals are not explained by mononucleotide composition but instead by how those nucleotides are arranged into short sequence motifs. These results suggest that lifespan and genome size show distinct but overlapping associations with regional sequence composition across invertebrate species and that lifespan-associated motif evolution extends beyond vertebrate promoter methylation architectures.

CpG density↗
PubMed2026

A tunable, ultrasensitive threshold in enzymatic activity governs the DNA methylation landscape.

DNA methylation is a widely studied epigenetic mark, affecting gene expression and cellular function at multiple levels. DNA methylation in the mammalian genome occurs primarily at cytosine-phosphate-guanine (CpG) dinucleotides, and patterning of the methylation landscape (i.e., the presence or absence of CpG methylation at a given genomic location) exhibits a generally bimodal distribution. Although much is known about the enzymatic writers and erasers of CpG methylation, it is not fully understood how these enzymes, along with genetic, chromatin, and regulatory factors, control the genome-wide methylation landscape. In this study, methylation is analyzed at annotated CpG islands (CGIs) and independent CpGs as a function of their proximity to other CpG substrates. Analysis is aided by a computationally efficient stochastic mathematical model of methylation dynamics, enabling parameterization from data. We find that methylation exhibits a switch-like dependence on local CpG density with a threshold of 7-8 CpGs per 100 bp and a Hill coefficient of 4-5. The threshold and steepness of the switch is modified in cell lines in which key enzymes are knocked out. Modeling further elucidates how enzymatic parameters, including catalytic rates and lengthscales of inter-CpG interaction, tune the properties of the switch. Together, the results support a model in which competition between opposing TET1-3 demethylating enzymes and DNA methyltransferases (DNMT3A/B) results in an ultrasensitive switch, analogous to the protein phosphorylation switch (termed "zero-order ultrasensitivity"). Our study provides insight to the mechanisms underlying establishment and maintenance of bimodal DNA methylation landscapes, and further provides a flexible pipeline for gleaning molecular insights to the cellular methylation machinery across cell-specific, epigenomic data sets.

DNA Methylation↗
PubMed2025

OpTiles: an R package for adaptive tiling and methylation variability profiling.

SUMMARY: OpTiles is an R package that dynamically defines tiling windows based on the distribution of sequenced CpGs, addressing the limitations of traditional fixed-tiling approaches in targeted methylation datasets. By integrating CpG density with intra-region methylation variability, it provides a reliability metric and extended functionality for annotating, prioritizing, and interpreting complex methylation data. AVAILABILITY AND IMPLEMENTATION: OpTiles is implemented in R and source code is freely available at https://github.com/fhaive/OpTiles. Data are available on Zenodo at https://doi.org/10.5281/zenodo.16961292.

DNA Methylation↗
PubMed2022

Temporal associations between leukocytes DNA methylation and blood lipids: a longitudinal study.

BACKGROUND: The associations between blood lipids and DNA methylation have been investigated in epigenome-wide association studies mainly among European ancestry populations. Several studies have explored the direction of the association using cross-sectional data, while evidence of longitudinal data is still lacking. RESULTS: We tested the associations between peripheral blood leukocytes DNA methylation and four lipid measures from Illumina 450 K or EPIC arrays in 1084 participants from the Chinese National Twin Registry and replicated the result in 988 participants from the China Kadoorie Biobank. A total of 23 associations of 19 CpG sites were identified, with 4 CpG sites located in or adjacent to 3 genes (TMEM49, SNX5/SNORD17 and CCDC7) being novel. Among the validated associations, we conducted a cross-lagged analysis to explore the temporal sequence and found temporal associations of methylation levels of 2 CpG sites with triglyceride and 2 CpG sites with high-density lipoprotein-cholesterol (HDL-C) in all twins. In addition, methylation levels of cg11024682 located in SREBF1 at baseline were temporally associated with triglyceride at follow-up in only monozygotic twins. We then performed a mediation analysis with the longitudinal data and the result showed that the association between body mass index and HDL-C was partially mediated by the methylation level of cg06500161 (ABCG1), with a mediation proportion of 10.1%. CONCLUSIONS: Our study indicated that the DNA methylation levels of ABCG1, AKAP1 and SREBF1 may be involved in lipid metabolism and provided evidence for elucidating the regulatory mechanism of lipid homeostasis.

Humans↗
PubMed1977

Adenosine triphosphatase activity associated with purified cholinergic synaptic vesicles of Torpedo marmorata.

A rapid method for purifying Torpedo electric organ vesicles is described, which employs an isoosmotic continuous sucrose-glycine gradient followed by chromagography on CPG-10-3000 porous glass beads. The synaptic vesicles have a buoyant density of 1.057 g/ml. The purified vesicles are free of cholinesterase, lactate dehydrogenase and Na+, K+-stimulated ATPase activity. They contain a ouabaininsensitive, Na+, K+-inhibited, Mg2+, Ca2+-stimulated ATPase activity. This is further stimulated by acetylcholine but not by choline.

Acetylcholine↗
PubMed1978

Purification of mengovirus by freon extraction and chromatography on protein-coated controlled pore glass.

Mengovirus, extracted from infected L-cell cultures with Freon 113 and concentrated from the aqueous phase with polyethyleneglycol, was chromatographed on protein-coated controlled pore glass (CPG). The covalent binding of protein to CPG is described. Further purification and concentration of mengovirus was achieved by isopycnic density gradient centrifugation in solutions of either CsCl or salts of iodinated benzoic acid derivatives. The described procedure is superior to conventional methods for the isolation and purification of large quantities of mengovirus. It yields highly purified virus preparations within a short time and a recovery of more than 50% of the starting infectivity.

Chemical Precipitation↗
PubMed2026

Interplay between the role of DNA methylation in regulating gene expression and TE-silencing in a reptilian methylome.

DNA methylation is a major component of eukaryotic genomes with an important role in the defence against transposable elements, to transcriptionally silence their activity and prevent transposition. DNA methylation also plays a major role in the regulation of gene expression. This dual role can come into conflict, where DNA methylation in gene regulatory regions becomes perturbed due to transposable element transposition, leading to disruption of gene expression. Here, we describe how this conflict is reflected in DNA methylation patterns in the sand lizard genome where there is recent transposable element activity. Using long-read sequencing technology we show that CpG islands in gene transcriptional start sites are typically hypomethylated and associated with higher gene expression. Outside transcriptional start sites, a majority of CpG islands overlapped transposable elements and were associated with hypermethylation, consistent with a host-defence role in suppressing transposition activity. We identify 605 instances where transcriptional start sites were associated with transposable elements (4.3% of all genes). These instances were far rarer in conjunction with a CpG island, when methylation signatures would be in conflict. Transposable elements were found to be closer to and at higher density the more hypermethylated a transcriptional start site was, suggesting strong selection against selfish genetic elements transposing into hypomethylated transcriptional start sites.

CpG islands↗
PubMed1979

Simple method to detect virus-specific IgM antibodies in patients' serum samples after immunosorption of immunoglobulins G and A.

By absorption with protein A and specific immunosorption using insolubilized adsorbentia (CPG), a method was developed for rapid elimination of IgG and IgA from patients' serum samples. This test technique was examined in the diagnosis of rubella infections, i.e., rubella-specific IgM antibodies. The procedure has proven to be as reliable as determinations carried out with IgM fractions separated on a sucroe density gradient.

Antibodies, Viral↗
PubMed1979

Nucleotide sequence of a highly repetitive component of rat DNA.

A highly repetitive component of rat DNA which could not yet be enriched by density gradient centrifugation was isolated with the help of the restriction nuclease Sau3AI. This nuclease converted the bulk of the DNA to small fragments and left a repetitive DNA component as large fragments which were subsequently purified by gel filtration and electrophoresis. This DNA component which was termed rat satellite DNA I is composed of tandemly repeated 370 bp blocks. According to sequence analysis the 370 bp repeats consist of alternating 92 and 93 bp units with homologous but not identical sequences. Methylation of CpG residues was correlated to the rate of cleavage by restriction nucleases. Significant homologies exist between the sequences of rat satellite DNA I and satellite DNAs of several other organisms. The divergence of the sequence of rat satellite DNA I was discussed with respect to evolutionary considerations.

Animals↗
PubMed2026

DNA methylation signatures in skeletal muscle associated with physical function in healthy older adults.

Despite the substantial variability in physical function among older adults, the molecular mechanisms remain poorly characterized, particularly within skeletal muscle. This study aimed to determine the patterns of DNA methylation in skeletal muscle associated with physical function in healthy older adults. We analyzed DNA methylation (EPIC v2 array; 875,554 CpG sites) in skeletal muscle from 92 healthy older adults (median age 74; 62% female). Associations were examined across five phenotypes: Short Physical Performance Battery (SPPB), 6-min walk test (6MWT), handgrip strength, perceived disability (PAT-D), and lifestyle health (modified Life's Essential 8). Linear regression models adjusted for age, sex, race, BMI, and muscle fiber composition. Genomic inflation corrected via the BACON method (FDR&#x2009;<&#x2009;0.05). Gene set enrichment analysis was performed on suggestive hits (FDR&#x2009;<&#x2009;0.1). We identified significant differentially methylated probes (DMPs) and regions (DMRs) across all phenotypes: SPPB (70 DMPs, 22 DMRs), 6MWT (16 DMPs, 566 DMRs), handgrip strength (2 DMRs), PAT-D (19 DMPs, 1 DMR), and lifestyle health (2 DMPs). DMRs largely overlapped promoters. Identified genes overlapped known musculoskeletal and neurological GWAS hits, including RUNX2 and FOXL1 (bone mineral density), IGFBP3 (muscle mass), and NEK1 and SHANK1 (neurological function). Enrichment analysis revealed that 6MWT-associated genes relate to nervous and skeletal system development, while handgrip-associated genes involve cytoskeletal dynamics and protein assembly. Epigenetic variation in aging skeletal muscle is associated with physical function. The enrichment of pathways related to nervous and musculoskeletal development suggests specific epigenetic mechanisms underlying functional decline, offering potential targets for intervention in older adults.

DNA methylation↗