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1. DNA Methylation in Ctenophores

   https://doi.org/10.1007/978-1-0716-3642-8_18  

   Dabe, Emily C; Kohn, Andrea B; Moroz, Leonid L (January 2024, Springer US)
2. Gene Expression and DNA Methylation in Human Papillomavirus Positive and Negative Head and Neck Squamous Cell Carcinomas

   https://doi.org/10.3390/ijms231810967  

   Hinić, Snežana; Rich, April; Anayannis, Nicole V.; Cabarcas-Petroski, Stephanie; Schramm, Laura; Meneses, Patricio I. (September 2022, International Journal of Molecular Sciences)

   High-risk human papillomaviruses (HPV) are important agents, responsible for a large percentage of the 745,000 cases of head and neck squamous cell carcinomas (HNSCC), which were identified worldwide in 2020. In addition to being virally induced, tobacco and heavy alcohol consumption are believed to cause DNA damage contributing to the high number of HNSCC cases. Gene expression and DNA methylation differ between HNSCC based on HPV status. We used publicly available gene expression and DNA methylation profiles from the Cancer Genome Atlas and compared HPV positive and HPV negative HNSCC groups. We used differential gene expression analysis, differential methylation analysis, and a combination of these two analyses to identify the differences. Differential expression analysis identified 1854 differentially expressed genes, including PCNA, TNFRSF14, TRAF1, TRAF2, BCL2, and BIRC3. SYCP2 was identified as one of the top deregulated genes in the differential methylation analysis and in the combined differential expression and methylation analyses. Additionally, pathway and ontology analyses identified the extracellular matrix and receptor interaction pathway as the most altered between HPV negative and HPV positive HNSCC groups. Combining gene expression and DNA methylation can help in elucidating the genes involved in HPV positive HNSCC tumorigenesis, such as SYCP2 and TAF7L. 

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3. Locally correlated kinetics of post-replication DNA methylation reveals processivity and region specificity in DNA methylation maintenance

   https://doi.org/10.1098/rsif.2022.0415  

   Ren, Honglei; Taylor, Robert B.; Downing, Timothy L.; Read, Elizabeth L. (October 2022, Journal of The Royal Society Interface)

   DNA methylation occurs predominantly on cytosine-phosphate-guanine (CpG) dinucleotides in the mammalian genome, and the methylation landscape is maintained over mitotic cell division. It has been posited that coupling of maintenance methylation activity among neighbouring CpGs is critical to stability over cellular generations; however, the mechanism is unclear. We used mathematical models and stochastic simulation to analyse data from experiments that probe genome-wide methylation of nascent DNA post-replication in cells. We find that DNA methylation maintenance rates on individual CpGs are locally correlated, and the degree of this correlation varies by genomic regional context. By using theory of protein diffusion along DNA, we show that exponential decay of methylation rate correlation with genomic distance is consistent with enzyme processivity. Our results provide quantitative evidence of genome-wide methyltransferase processivity in vivo . We further developed a method to disentangle different mechanistic sources of kinetic correlations. From the experimental data, we estimate that an individual methyltransferase methylates neighbour CpGs processively if they are 36 basepairs apart, on average. But other mechanisms of coupling dominate for longer inter-CpG distances. Our study demonstrates that quantitative insights into enzymatic mechanisms can be obtained from replication-associated, cell-based genome-wide measurements, by combining data-driven statistical analyses with hypothesis-driven mathematical modelling. 

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4. DNA methylation networks underlying mammalian traits

   https://doi.org/10.1126/science.abq5693  

   Haghani, Amin; Li, Caesar Z.; Robeck, Todd R.; Zhang, Joshua; Lu, Ake T.; Ablaeva, Julia; Acosta-Rodríguez, Victoria A.; Adams, Danielle M.; Alagaili, Abdulaziz N.; Almunia, Javier; et al (August 2023, Science)

   Using DNA methylation profiles (n= 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels inHOXLsubclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species. 

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5. Evolution of DNA methylation in the human brain

   https://doi.org/10.1038/s41467-021-21917-7  

   Jeong, Hyeonsoo; Mendizabal, Isabel; Berto, Stefano; Chatterjee, Paramita; Layman, Thomas; Usui, Noriyoshi; Toriumi, Kazuya; Douglas, Connor; Singh, Devika; Huh, Iksoo; et al (December 2021, Nature Communications)

   null (Ed.)

   Abstract DNA methylation is a critical regulatory mechanism implicated in development, learning, memory, and disease in the human brain. Here we have elucidated DNA methylation changes during recent human brain evolution. We demonstrate dynamic evolutionary trajectories of DNA methylation in cell-type and cytosine-context specific manner. Specifically, DNA methylation in non-CG context, namely CH methylation, has increased (hypermethylation) in neuronal gene bodies during human brain evolution, contributing to human-specific down-regulation of genes and co-expression modules. The effects of CH hypermethylation is particularly pronounced in early development and neuronal subtypes. In contrast, DNA methylation in CG context shows pronounced reduction (hypomethylation) in human brains, notably in cis-regulatory regions, leading to upregulation of downstream genes. We show that the majority of differential CG methylation between neurons and oligodendrocytes originated before the divergence of hominoids and catarrhine monkeys, and harbors strong signal for genetic risk for schizophrenia. Remarkably, a substantial portion of differential CG methylation between neurons and oligodendrocytes emerged in the human lineage since the divergence from the chimpanzee lineage and carries significant genetic risk for schizophrenia. Therefore, recent epigenetic evolution of human cortex has shaped the cellular regulatory landscape and contributed to the increased vulnerability to neuropsychiatric diseases. 

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