Publications by authors named "Noah Kessler"
Article Synopsis
- Metastable epialleles (MEs) are DNA regions where methylation levels vary among individuals but remain consistent across different tissues in the same person, potentially influenced by environmental factors.
- This review covers the definition of MEs, techniques for identifying them in humans, and their genetic characteristics.
- It also examines research connecting DNA methylation at these MEs to early environmental influences and later health outcomes.
Article Synopsis
- DNA methylation at CpG sites is typically viewed as a stable epigenetic marker, but new research shows its inheritance is more complex than previously thought.
- High-throughput bisulfite sequencing revealed that while methylation is generally stable at low and high levels, intermediate methylation does not maintain this stability consistently across the genome.
- The study suggests that changes in intermediate methylation are likely influenced by the enzyme DNMT1 and challenges the conventional understanding of DNA methylation as a reliable marker for epigenetic inheritance, raising questions about its functional significance.
Article Synopsis
- Human height is primarily determined by genetics, but this study explores how modifiable epigenetic factors, specifically blood DNA methylation, influence child height in low and middle-income countries (LMIC).
- The research identifies a significant link between DNA methylation in the SOCS3 gene and child height, with findings replicating in a high-income country cohort, showing that this effect is independent of genetic factors.
- Analysis reveals that SOCS3 methylation explains up to 9.5% of height variance in mid-childhood and is influenced by prenatal maternal folate and socio-economic status, highlighting the potential role of epigenetic modifications in child growth in LMIC.
Article Synopsis
- Human neonates experience a significant decrease in serum iron levels right after birth, which seems to offer protection against bacterial infections.
- In a study of 278 Gambian newborns, blood samples were taken to analyze various iron and inflammation markers over the first week, revealing that both serum iron and transferrin saturation rose steadily from their low levels by day 7.
- The results highlighted that this early iron deficiency is consistent yet temporary, with hepcidin levels initially rising and then showing variations, suggesting some level of resistance to its effects as iron levels start to recover.
Article Synopsis
- The study examined DNA methylation across 30 datasets with 3474 individuals from various tissues and ethnicities, identifying 4143 highly variable methylation sites (hvCpGs).
- These hvCpGs were influenced by genetic factors but were not solely determined by them, nor were they significantly affected by factors like age, sex, or cell differences.
- The hvCpGs showed patterns linking to retrovirus elements and were associated with early environmental factors, making them important for studying how early DNA methylation may affect long-term health.
Article Synopsis
- DNA methylation patterns from parents are mostly erased after fertilization, which influences the embryo's development and marks for gene expression.* -
- A study in rural Gambia analyzed data from children conceived in different seasons, finding 259 specific DNA regions (CpGs) linked to the season of conception (SoC), especially evident in early infancy.* -
- These findings suggest that the environment around conception plays a significant role in shaping long-lasting epigenetic changes that may impact health throughout life.*
PAX8 is a key thyroid transcription factor implicated in thyroid gland differentiation and function, and gene methylation is reported to be sensitive to the periconceptional environment. Using a novel recall-by-epigenotype study in Gambian children, we found that hypomethylation at age 2 years is associated with a 21% increase in thyroid volume and an increase in free thyroxine (T4) at 5 to 8 years, the latter equivalent to 8.4% of the normal range.
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- Transposable elements (TEs), especially intracisternal A particle (IAP) TEs in mice, have varying levels of cytosine methylation, influencing their activity and genomic function.
- The study reveals two classes of IAPs: tissue-specific variable methylation (tsVM-IAPs) and those with consistent methylation across tissues (cVM-IAPs), both capable of regulating nearby genes.
- Findings suggest that genetic sequences, CTCF binding, and DNA methylation interplay to create individual differences in gene expression, potentially leading to variations in traits and phenotypes.
Septicemia is a leading cause of death among neonates in low-income settings, a situation that is deteriorating due to high levels of antimicrobial resistance. Novel interventions are urgently needed. Iron stimulates the growth of most bacteria and hypoferremia induced by the acute phase response is a key element of innate immunity.
View Article and Find Full Text PDFPancreatic islets of type 2 diabetes patients have altered DNA methylation, contributing to islet dysfunction and the onset of type 2 diabetes. The cause of these epigenetic alterations is largely unknown. We set out to test whether (i) islet DNA methylation would change with aging and (ii) early postnatal overnutrition would persistently alter DNA methylation.
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- DNA methylation plays a key role in human phenotypic variation, but its impact has been difficult to measure due to its specificity to different cell types.
- Researchers identified 9,926 genomic regions (CoRSIVs) demonstrating consistent interindividual DNA methylation variation across three germ layer tissues—thyroid, heart, and brain.
- These CoRSIVs are linked to human disease and phenotypes, offering a valuable resource for studying how epigenetic differences may influence individual health risks in the future.
Iron deficiency anemia (IDA) is the most prevalent nutritional condition worldwide. We studied the contribution of hepcidin-mediated iron blockade to IDA in African children. We measured hepcidin and hemoglobin weekly, and hematological, inflammatory, and iron biomarkers at baseline, 7 weeks, and 12 weeks in 407 anemic (hemoglobin < 11 g/dl), otherwise healthy Gambian children (6 to 27 months).
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- - The study explores how women's nutrition before conception affects their children's DNA methylation, specifically at metastable epialleles (MEs), which are unique genomic regions that vary in methylation patterns.
- - Researchers conducted a genome-wide analysis identifying 687 MEs, revealing irregular methylation changes during critical developmental stages in IVF embryos, indicating potential responsiveness to environmental influences.
- - In a case study from rural Gambia, MEs associated with seasonal conception displayed similar unusual methylation patterns, suggesting that these epigenetic markers are shaped by both genetic factors and the pre-conception environment, potentially impacting offspring traits.
Article Synopsis
- Monozygotic twins are often studied to understand the role of genetics and epigenetics in their phenotypic similarities, which are thought to be mainly due to their identical genetics.
- Recent research shows that monozygotic twins have greater epigenetic similarity than expected, due to specific epigenetic changes happening before the embryo splits, a phenomenon called "epigenetic supersimilarity."
- This epigenetic similarity is linked to environmental factors and is associated with a higher risk of developing certain cancers, suggesting early embryonic epigenetic changes can influence health later in life.
Article Synopsis
- - The study explores differences in DNA methylation between neurons and glia, highlighting that prior research downplayed the role of CpG methylation and focused on non-CpG methylation instead.
- - The authors reanalyze data and discover significant cell type-specific differences in CpG methylation, with distinct patterns of hypermethylation for neurons and glia.
- - Their findings emphasize the importance of verifying epigenetic research and suggest that CpG methylation is crucial in neuroepigenetics, supporting the mouse model for studying human neurodevelopment and disease.
Article Synopsis
- The research investigates how early environmental factors influence epigenetic changes in the embryo, particularly focusing on differentially methylated regions in easily accessible tissues like blood and hair follicles.
- Two methods were used: genome-wide bisulfite sequencing in adults' DNA and assessing PBL methylation differences related to the season of conception in rural Gambia, both revealing the VTRNA2-1 gene as a primary epigenetic responder to environmental changes.
- The findings suggest that the VTRNA2-1 gene, linked to immunity and cancer suppression, experiences stable epigenetic changes due to early environmental conditions, highlighting potential connections between these alterations and human health outcomes.
Environmental factors affecting nutrient availability during development can cause predisposition to diseases later in life. To identify chemicals in the environment capable of altering nutrient mobilization, we analyzed yolk malabsorption in the zebrafish embryo, which relies on maternally-derived yolk for nutrition during its first week of life. Embryos of the transgenic zebrafish line HGn50D, which fluoresce in the yolk syncytial layer, were exposed from two to five days post fertilization to different chemicals.
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- Coupling bisulfite conversion with next-gen sequencing allows for DNA methylation measurement, but mapping presents challenges.
- A study compared five Bisulfite-seq mapping tools (Bismark, BSMAP, Pash, BatMeth, and BS Seeker) in terms of computational speed, genomic coverage, and methylation accuracy using DNA from two healthy adults.
- Results showed that most tools covered over 70% of CpG sites with high accuracy, but Bismark offered a good balance of speed and coverage, while Pash excelled in coverage, particularly in regions with structural variation.