| 1. |
- Aberg, KA, et al.
(författare)
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MBD-seq as a cost-effective approach for methylome-wide association studies: demonstration in 1500 case--control samples
- 2012
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 4:6, s. 605-621
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Tidskriftsartikel (refereegranskat)abstract
- Aim: We studied the use of methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq) as a cost-effective screening tool for methylome-wide association studies (MWAS). Materials & methods: Because MBD-seq has not yet been applied on a large scale, we first developed and tested a pipeline for data processing using 1500 schizophrenia cases and controls plus 75 technical replicates with an average of 68 million reads per sample. This involved the use of technical replicates to optimize quality control for multi- and duplicate-reads, an in silico experiment to identify CpGs in loci with alignment problems, CpG coverage calculations based on multiparametric estimates of the fragment size distribution, a two-stage adaptive algorithm to combine data from correlated adjacent CpG sites, principal component analyses to control for confounders and new software tailored to handle the large data set. Results: We replicated MWAS findings in independent samples using a different technology that provided single base resolution. In an MWAS of age-related methylation changes, one of our top findings was a previously reported robust association involving GRIA2. Our results also suggested that owing to the many confounding effects, a considerable challenge in MWAS is to identify those effects that are informative about disease processes. Conclusion: This study showed the potential of MBD-seq as a cost-effective tool in large-scale disease studies.
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| 2. |
- Altintas, A, et al.
(författare)
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Transcriptomic and epigenomics atlas of myotubes reveals insight into the circadian control of metabolism and development
- 2020
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 12:8, s. 701-713
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Innate circadian rhythms are critical for optimal tissue-specific functions, including skeletal muscle, a major insulin-sensitive tissue responsible for glucose homeostasis. We determined whether transcriptional oscillations are associated with CpG methylation changes in skeletal muscle. Materials & methods: We performed rhythmicity analysis on the transcriptome and CpG methylome of circadian synchronized myotubes. Results: We identified several transcripts and CpG-sites displaying oscillatory behavior, which were enriched with Gene Ontology terms related to metabolism and development. Oscillating CpG methylation was associated with rhythmic expression of 31 transcripts. Conclusion: Although circadian oscillations may be regulated by rhythmic DNA methylation, strong rhythmic associations between transcriptome and CpG methylation were not identified. This resource constitutes a transcriptomic/epigenomic atlas of skeletal muscle and regulation of circadian rhythms.
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| 3. |
- Andersen, E., et al.
(författare)
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Environmental factors influence the epigenetic signature of newborns from mothers with gestational diabetes
- 2019
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 11:8, s. 861-873
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate the degree by which epigenetic signatures in children from mothers with gestational diabetes mellitus (GDM) are influenced by environmental factors. Methods: We profiled the DNA methylation signature of blood from lean, obese and GDM mothers and their respective newborns. Results: DNA methylation profiles of mothers showed high similarity across groups, while newborns from GDM mothers showed a marked distinct epigenetic profile compared with newborns of both lean and obese mothers. Analysis of variance in DNA methylation levels between newborns showed higher variance in the GDM group. Conclusion: Our results suggest that environmental factors, rather than direct transmission of epigenetic marks from the mother, are involved in establishing the epigenetic signature associated with GDM. © 2019 Romain Barrès.
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| 4. |
- Broholm, Christa, et al.
(författare)
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Human adipogenesis is associated with genome-wide DNA methylation and gene-expression changes
- 2016
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 8:12, s. 1601-1617
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To define the genomic distribution and function of DNA methylation changes during human adipogenesis. Methods: We isolated adipocyte-derived stem cells from 13 individuals and analyzed genome-wide DNA methylation and gene expression in cultured adipocyte-derived stem cells and mature adipocytes. Results: We observed altered DNA methylation of 11,947 CpG sites and altered expression of 11,830 transcripts after differentiation. De novo methylation was observed across all genomic elements. Co-existence of genes with both altered expression and DNA methylation was found in genes important for cell cycle and adipokine signaling. Conclusion: Human adipogenesis is associated with significant DNA methylation changes across the entire genome and may impact regulation of cell cycle and adipokine signaling.
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| 5. |
- Bysani, Madhusudhan, et al.
(författare)
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Epigenetic alterations in blood mirror age-associated DNA methylation and gene expression changes in human liver
- 2017
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 9:2, s. 105-122
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study the impact of aging on DNA methylation and mRNA expression in human liver. Experimental procedures: We analysed genome-wide DNA methylation and gene expression in human liver samples using Illumina 450K and HumanHT12 expression BeadChip arrays. Results: DNA methylation analysis of ∼455,000 CpG sites in human liver revealed that age was significantly associated with altered DNA methylation of 20,396 CpG sites. Comparison of liver methylation data with published methylation data in other tissues showed that vast majority of the age-associated significant CpG sites overlapped between liver and blood, whereas a smaller overlap was found between liver and pancreatic islets or adipose tissue, respectively. We identified 151 genes whose liver expression also correlated with age. Conclusions: We identified age-associated DNA methylation and expression changes in human liver that are partly reflected by epigenetic alterations in blood.
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| 6. |
- Cartron, PF, et al.
(författare)
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Epigenetic protein complexes: the adequate candidates for the use of a new generation of epidrugs in personalized and precision medicine in cancer
- 2020
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 12:2, s. 171-177
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Tidskriftsartikel (refereegranskat)abstract
- Until recently, drug development in oncology was focused on treating most patients for a specific cancer type without taking in account the heterogeneity between these patients in term of response to treatment. Therefore, this type of broad treatment approach excludes the treatment of patient not responding to disease-specific common drugs. In this review, we focus on the different types of epigenetic drugs currently used as DNA methylation inhibitor agents and their limits in patient care due to their lack of specificity. We also highlight the emergence of a new type of epidrug with higher target specificity due to their original mechanism of action: the disruption of protein complexes involved in the epigenetic modifications.
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| 7. |
- Chilunga, FP, et al.
(författare)
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DNA methylation as the link between migration and the major noncommunicable diseases: the RODAM study
- 2021
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 13:099, s. 653-666
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Tidskriftsartikel (refereegranskat)abstract
- Aim: We assessed epigenome-wide DNA methylation (DNAm) differences between migrant and non-migrant Ghanaians. Materials & methods: We used the Illumina Infinium® HumanMethylation450 BeadChip to profile DNAm of 712 Ghanaians in whole blood. We used linear models to detect differentially methylated positions (DMPs) associated with migration. We performed multiple post hoc analyses to validate our findings. Results: We identified 13 DMPs associated with migration (delta-beta values: 0.2–4.5%). Seven DMPs in CPLX2, EIF4E3, MEF2D, TLX3, ST8SIA1, ANG and CHRM3 were independent of extrinsic genomic influences in public databases. Two DMPs in NLRC5 were associated with duration of stay in Europe among migrants. All DMPs were biologically linked to migration-related factors. Conclusion: Our findings provide the first insights into DNAm differences between migrants and non-migrants.
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| 8. |
- Chouliaras, Leonidas, et al.
(författare)
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DNMT3A moderates cognitive decline in subjects with mild cognitive impairment: replicated evidence from two mild cognitive impairment cohorts.
- 2015
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 7:4, s. 533-537
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic dysregulation has been associated with cognitive decline and Alzheimer's disease. The present study investigated associations between common SNPs in genes regulating DNA methylation and age-related changes in cognitive decline in two independent prospective cohorts of patients suffering from mild cognitive impairment. An association between the rs1187120 SNP in DNMT3A and annual decline in cognitive functioning was discovered and replicated, suggesting that DNMT3A moderates cognitive decline in subjects with mild cognitive impairment.
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| 9. |
- Davidsson, Josef
(författare)
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The epigenetic landscape of aneuploidy: constitutional mosaicism leading the way?
- 2014
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 6:1, s. 45-58
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Tidskriftsartikel (refereegranskat)abstract
- The role of structural genetic changes in human disease has received substantial attention in recent decades, but surprisingly little is known about numerical chromosomal abnormalities, even though they have been recognized since the days of Boveri as partaking in different cellular pathophysiological processes such as cancer and genomic disorders. The current knowledge of the genetic and epigenetic consequences of aneuploidy is reviewed herein, with a special focus on using mosaic genetic syndromes to study the DNA methylation footprints and expressional effects associated with whole-chromosomal gains. Recent progress in understanding the debated role of aneuploidy as a driver or passenger in malignant transformation, as well as how the cell responds to and regulates excess genetic material in experimental settings, is also discussed in detail.
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| 10. |
- Ek, Weronica E., et al.
(författare)
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Epigenome-wide DNA methylation study of IgE concentration in relation to self-reported allergies
- 2017
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 9:4, s. 407-418
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Epigenetic mechanisms are critical for normal immune development and epigenetic alterations might therefore be possible contributors to immune diseases. To investigate if DNA methylation in whole blood is associated with total and allergen-specific IgE levels.METHODS: We performed an epigenome-wide association study to investigate the association between DNA methylation and IgE level, allergen-specific IgE and self-reported immune diseases and allergies in 728 individuals.RESULTS: We identified and replicated 15 CpG sites associated with IgE, mapping to biologically relevant genes, including ACOT7, ILR5A, KCNH2, PRG2 and EPX. A total of 331 loci were associated with allergen-specific IgE, but none of these CpG sites were associated with self-reported allergies and immune diseases.CONCLUSION: This study shows that IgE levels are associated with DNA methylation levels at numerous CpG sites, which might provide new leads for investigating the links between IgE and allergic inflammation.
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| 11. |
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| 12. |
- Fernandes, SJ, et al.
(författare)
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Deep characterization of paired chromatin and transcriptomes in four immune cell types from multiple sclerosis patients
- 2021
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 13:20, s. 1607-1618
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Tidskriftsartikel (refereegranskat)abstract
- Background: The putative involvement of chromatin states in multiple sclerosis (MS) is thus far unclear. Here we determined the association of chromatin-accessibility with concurrent genetic, epigenetic and transcriptional events. Material & methods: We generated paired assay for transposase-accessible chromatin sequencing and RNA-sequencing profiles from sorted blood immune CD4+ and CD8+ T cells, CD14+ monocytes and CD19+ B cells from healthy controls (HCs) and MS patients. Results: We identified differentially accessible regions between MS patients and HCs, primarily in CD4+ and CD19+. CD4+ regions were enriched for MS-associated single nucleotide polymorphisms and differentially methylated loci. In the vicinity of differentially accessible regions of CD4+ cells, 42 differentially expressed genes were identified. The top two dysregulated genes identified in this multilayer analysis were CCDC114 and SERTAD1. Conclusion: These findings provide new insight into the primary role of CD4+ and CD19+ cells in MS.
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| 13. |
- Fragoso-Bargas, Nicolas, et al.
(författare)
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Epigenome-wide association study of serum folate in maternal peripheral blood leukocytes
- 2023
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 15:1, s. 39-52
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To perform an epigenome-wide association study (EWAS) of serum folate in maternal blood. Methods: Cross-ancestry (Europeans = 302, South Asians = 161) and ancestry-specific EWAS in the EPIPREG cohort were performed, followed by methyl quantitative trait loci analysis and association with cardiometabolic phenotypes. Replication was attempted using maternal folate intake and blood methylation data from the MoBa study and verified if the findings were significant in a previous EWAS of maternal serum folate in cord blood. Results & conclusion: cg19888088 (cross-ancestry) in EBF3, cg01952260 (Europeans) and cg07077240 (South Asians) in HERC3 were associated with serum folate. cg19888088 and cg01952260 were associated with diastolic blood pressure. cg07077240 was associated with variants in CASC15. The findings were not replicated and were not significant in cord blood.
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| 14. |
- Karlsson, Oskar
(författare)
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Epigenetics in the Anthropocene : an interview with Oskar Karlsson
- 2022
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 14:6, s. 315-318
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this interview, Oskar Karlsson speaks with Storm Johnson, commissioning editor for Epigenomics, on his work to date in the field of toxicological origins of disease and gene-environment interactions. Oskar Karlsson, is an associate professor at the Science for Life Laboratory (SciLifeLab), Department of Environmental Science, Stockholm University, Sweden. Dr. Karlsson earned a PhD in toxicology at the Department of Pharmaceutical Bioscience, Uppsala University, and has also worked at Centre of Molecular Medicine, Karolinska Institute, as well as Harvard University School of Public Health. His research combines experimental model systems, computational and omics tools, and epidemiological studies to investigate the influence of environmental exposures on wildlife and human health, and underlying molecular mechanisms. In particular, his research focuses on developmental origins of health and disease with an emphasis on environmental exposures and epigenetic mechanisms. The projects concern the effects of exposures such as endocrine disrupting chemicals, flame retardants, pesticides, metals and particulate air pollution, as well as drugs, psycho-social stressors and ethnical disparities. Ongoing efforts include studies of paternal epigenetic inheritance in the ERC-funded project PATER.
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| 15. |
- Levin-Schwartz, Yuri, et al.
(författare)
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Exosomal miRNAs in urine associated with children's cardiorenal parameters : A cross-sectional study
- 2021
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Ingår i: Epigenetics. - : Future Medicine Ltd. - 1559-2294 .- 1559-2308. ; 13:7, s. 499-512
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The authors sought to examine associations between urinary exosomal miRNAs (exo-miRs), emerging biomarkers of renal health, and cardiorenal outcomes in early childhood. Materials & Methods: The authors extracted exo-miRs in urine from 88 healthy Mexican children aged 4-6 years. The authors measured associations between 193 exo-miRs and cardiorenal outcomes: systolic/diastolic blood pressure, estimated glomerular filtration rate and urinary sodium and potassium levels. The authors adjusted for age, sex, BMI, socioeconomic status, indoor tobacco smoke exposure and urine specific gravity. Results: Multiple exo-miRs were identified meeting a false discovery rate threshold of q < 0.1. Specifically, three exo-miRs had increased expression with urinary sodium, 17 with urinary sodium-to-potassium ratio and one with decreased estimated glomerular filtration rate. Conclusions: These results highlight urinary exo-miRs as early-life biomarkers of children's cardiorenal health.
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| 16. |
- Manente, AG, et al.
(författare)
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KDM6B histone demethylase is an epigenetic regulator of estrogen receptor β expression in human pleural mesothelioma
- 2016
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 8:9, s. 1227-1238
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To assess the correlation between KDM6B and estrogen receptor β (ERβ) expression in malignant pleural mesothelioma (MPM). Materials & methods: We evaluated gene expression by in silico analysis of microarray data, real-time PCR and western blot in MPM tumors and cell lines. Results & conclusion: We report a strong positive correlation between the expression of KDM6B and ERβ in MPM tumors and cell lines. We describe that, in hypoxia, the HIF2α–KDM6B axis induces an epithelioid morphology and ERβ expression in biphasic MPM cells with estrogen receptor-negative phenotype. Reduced histone H3K27 tri-methylation confirms KDM6B activity under hypoxic conditions. Importantly, cells treated during reoxygenation with the selective ERβ agonist, KB9520, maintain ERβ expression and the less aggressive phenotype acquired in hypoxia.
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| 17. |
- Marttila, S, et al.
(författare)
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Methylation status of VTRNA2-1/nc886 is stable across populations, monozygotic twin pairs and in majority of tissues
- 2022
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 14:18, s. 1105-1124
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Tidskriftsartikel (refereegranskat)abstract
- Aims & methods: The aim of this study was to characterize the methylation level of a polymorphically imprinted gene, VTRNA2-1/ nc886, in human populations and somatic tissues.48 datasets, consisting of more than 30 tissues and >30,000 individuals, were used. Results: nc886 methylation status is associated with twin status and ethnic background, but the variation between populations is limited. Monozygotic twin pairs present concordant methylation, whereas ∼30% of dizygotic twin pairs present discordant methylation in the nc886 locus. The methylation levels of nc886 are uniform across somatic tissues, except in cerebellum and skeletal muscle. Conclusion: The nc886 imprint may be established in the oocyte, and, after implantation, the methylation status is stable, excluding a few specific tissues.
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| 18. |
- Meng, L, et al.
(författare)
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Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study
- 2021
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 13:12, s. 939-951
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Alcohol intake alters DNA methylation profiles and methylation might mediate the association between alcohol and disease, but limited number of positive CpG sites repeatedly replicated. Materials & methods: In total, 57 monozygotic (MZ) twin pairs discordant for alcohol drinking from the Chinese National Twin Registry and 158 MZ and dizygotic twin pairs in the Swedish Adoption/Twin Study of Aging were evaluated. DNA methylation was detected using the Infinium HumanMethylation450 BeadChip. Results: Among candidate CpG sites, cg07326074 was significantly correlated with drinking after adjusting for covariates in MZ twins in both datasets but not in the entire sample or dizygotic twins. Conclusion: The hypermethylation of cg07326074, located in the tumor-promoting gene C16orf59, was associated with alcohol consumption.
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| 19. |
- Parrillo, L., et al.
(författare)
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Altered PTPRD DNA methylation associates with restricted adipogenesis in healthy first-degree relatives of Type 2 diabetes subjects
- 2020
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 12:10, s. 873-888
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Tidskriftsartikel (refereegranskat)abstract
- Aim: First-degree relatives (FDR) of individuals with Type 2 diabetes (T2D) feature restricted adipogenesis, which render them more vulnerable to T2D. Epigenetics may contribute to these abnormalities. Methods: FDR pre-adipocyte Methylome and Transcriptome were investigated by MeDIP- and RNA-Seq, respectively. Results:Methylome analysis revealed 2841 differentially methylated regions (DMR) in FDR. Most DMR localized into gene-body and were hypomethylated. The strongest hypomethylation signal was identified in an intronic-DMR at the PTPRD gene. PTPRD hypomethylation in FDR was confirmed by bisulphite sequencing and was responsible for its upregulation. Interestingly, Ptprd-overexpression in 3T3-L1 pre-adipocytes inhibited adipogenesis. Notably, the validated PTPRD-associated DMR was significantly hypomethylated in peripheral blood leukocytes from the same FDR individuals. Finally, PTPRD methylation pattern was also replicated in obese individuals. Conclusion: Our findings indicated a previously unrecognized role of PTPRD in restraining adipogenesis. This abnormality may contribute to increase FDR proclivity toward T2D.
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| 20. |
- Rounge, TB, et al.
(författare)
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Genome-wide DNA methylation in saliva and body size of adolescent girls
- 2016
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 8:11, s. 1495-1505
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Tidskriftsartikel (refereegranskat)abstract
- Aim: We performed an epigenome-wide association study within the Finnish Health in Teens cohort to identify differential DNA methylation and its association with BMI in adolescents. Materials & methods: Differential DNA methylation analyses of 3.1 million CpG sites were performed in saliva samples from 50 lean and 50 heavy adolescent girls by genome-wide targeted bisulfite-sequencing. Results: We identified 100 CpG sites with p-values < 0.000524, seven regions by ‘bumphunting’ and five CpG islands that differed significantly between the two groups. The ten CpG sites and regions most strongly associated with BMI substantially overlapped with obesity- and insulin-related genes, including MC2R, IGFBPL1, IP6K1 and IGF2BP1. Conclusion: Our findings suggest an association between the saliva methylome and BMI in adolescence.
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| 21. |
- Rönn, Tina, et al.
(författare)
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DNA methylation as a diagnostic and therapeutic target in the battle against Type 2 diabetes.
- 2015
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 7:3, s. 451-460
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Forskningsöversikt (refereegranskat)abstract
- Type 2 diabetes (T2D) develops due to insulin resistance and impaired insulin secretion, predominantly in genetically predisposed subjects exposed to nongenetic risk factors like obesity, physical inactivity and ageing. Emerging data suggest that epigenetics also play a key role in the pathogenesis of T2D. Genome-wide studies have identified altered DNA methylation patterns in pancreatic islets, skeletal muscle and adipose tissue from subjects with T2D compared with nondiabetic controls. Environmental factors known to affect T2D, including obesity, exercise and diet, have also been found to alter the human epigenome. Additionally, ageing and the intrauterine environment are associated with differential DNA methylation. Together, these data highlight a key role for epigenetics and particularly DNA methylation in the growing incidence of T2D.
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| 22. |
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| 23. |
- Schrader, Silja, et al.
(författare)
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Statin therapy is associated with epigenetic modifications in individuals with Type 2 diabetes
- 2021
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 13:12, s. 919-925
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Statins lower cholesterol and reduce the risk of cardiovascular disease. However, the exact mechanisms of statins remain unknown. We investigated whether statin therapy associates with epigenetics in Type 2 diabetes (T2D) patients. Materials & methods: DNA methylation was analyzed in blood from newly diagnosed T2D patients in All New Diabetics in Scania (ANDIS) and a replication cohort All New Diabetics in Uppsala County (ANDiU). Results: Seventy-nine sites were differentially methylated between cases on statins and controls (false discovery rate <5%) in ANDIS. These include previously statin-associated methylation sites annotated to DHCR24 (cg17901584), ABCG1 (cg27243685) and SC4MOL (cg05119988). Differential methylation of two sites related to cholesterol biosynthesis and immune response, cg17901584 (DHCR24) and cg23011663 (ARIH2), were replicated in ANDiU. Conclusion: Statin therapy associates with epigenetic modifications in T2D patients.
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| 24. |
- Sikdar, S, et al.
(författare)
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Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking
- 2019
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 11:13, s. 1487-1500
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for in utero exposure in newborns is unknown. Materials & methods: We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and personal smoking (16 cohorts, 15907 participants, 2433 current smokers). Results & conclusion: Comparing meta-analyses, we identified numerous signatures specific to newborns along with many shared between newborns and adults. Unique smoking-associated genes in newborns were enriched in xenobiotic metabolism pathways. Our findings may provide insights into specific health impacts of prenatal exposure on offspring.
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| 25. |
- Sinha, I, et al.
(författare)
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Genome-wide mapping of histone modifications and mass spectrometry reveal H4 acetylation bias and H3K36 methylation at gene promoters in fission yeast
- 2010
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 2:3, s. 377-393
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To map histone modifications with unprecedented resolution both globally and locus-specifically, and to link modification patterns to gene expression. Materials & methods: Using correlations between quantitative mass spectrometry and chromatin immunoprecipitation/microarray analyses, we have mapped histone post-translational modifications in fission yeast (Schizosaccharomyces pombe). Results: Acetylations at lysine 9, 18 and 27 of histone H3 give the best positive correlations with gene expression in this organism. Using clustering analysis and gene ontology search tools, we identified promoter histone modification patterns that characterize several classes of gene function. For example, gene promoters of genes involved in cytokinesis have high H3K36me2 and low H3K4me2, whereas the converse pattern is found ar promoters of gene involved in positive regulation of the cell cycle. We detected acetylation of H4 preferentially at lysine 16 followed by lysine 12, 8 and 5. Our analysis shows that this H4 acetylation bias in the coding regions is dependent upon gene length and linked to gene expression. Our analysis also reveals a role for H3K36 methylation at gene promoters where it functions in a crosstalk between the histone methyltransferase Set2KMT3 and the histone deacetylase Clr6, which removes H3K27ac leading to repression of transcription. Conclusion: Histone modification patterns could be linked to gene expression in fission yeast.
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| 26. |
- Theodoropoulou, E, et al.
(författare)
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Different epigenetic clocks reflect distinct pathophysiological features of multiple sclerosis
- 2019
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 11:12, s. 1429-1439
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Accumulating evidence links epigenetic age to diseases and age-related conditions, but little is known about its association with multiple sclerosis (MS). Materials & methods: We estimated epigenetic age acceleration measures using DNA methylation from blood or sorted cells of MS patients and controls. Results: In blood, sex (p = 4.39E-05) and MS (p = 2.99E-03) explained the variation in age acceleration, and isolated blood cell types showed different epigenetic age. Intrinsic epigenetic age acceleration and extrinsic epigenetic age acceleration were only associated with sex (p = 2.52E-03 and p = 1.58E-04, respectively), while PhenoAge Acceleration displayed positive association with MS (p = 3.40E-02). Conclusion: Different age acceleration measures are distinctly influenced by phenotypic factors, and they might measure separate pathophysiological aspects of MS. Data deposition: DNA methylation data can be accessed at Gene Expression Omnibus database under accession number GSE35069, GSE43976, GSE106648, GSE130029, GSE130030.
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| 27. |
- Vymetalkova, Veronika, et al.
(författare)
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Epigenome-wide analysis of DNA methylation reveals a rectal cancer-specific epigenomic signature
- 2016
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Ingår i: Epigenomics. - London, United Kingdom : Future Medicine Ltd.. - 1750-1911 .- 1750-192X. ; 8:9, s. 1193-1207
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of the present study is to address a genome-wide search for novel methylation biomarkers in the rectal cancer (RC), as only scarce information on methylation profile is available.Materials and methods: We analyzed methylation status in 25 pairs of RC and adjacent healthy mucosa using the Illumina Human Methylation 450 BeadChip.Results: We found significantly aberrant methylation in 33 genes. After validation of our results by pyrosequencing, we found a good agreement with our findings. The BPIL3 and HBBP1 genes resulted hypomethylated in RC, whereas TIFPI2, ADHFE1, FLI1 and TLX1 were hypermethylated. An external validation by TCGA datasets confirmed the results.Conclusion: Our study, with external validation, has demonstrated the feasibility of using specific methylated DNA signatures for developing biomarkers in RC.
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| 28. |
- Wahlberg, Per, et al.
(författare)
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DNA methylome analysis of acute lymphoblastic leukemia cells reveals stochastic de novo DNA methylation in CpG islands
- 2016
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 8:10, s. 1367-1387
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To identify regions of aberrant DNA methylation in acute lymphoblastic leukemia (ALL) cells of different subtypes on a genome-wide scale. Materials & methods: Whole-genome bisulfite sequencing (WGBS) was used to determine the DNA methylation levels in cells from four pediatric ALL patients of different subtypes. The findings were confirmed by 450k DNA methylation arrays in a large patient set. Results: Compared with mature B or T cells WGBS detected on average 82,000 differentially methylated regions per patient. Differentially methylated regions are enriched to CpG poor regions, active enhancers and transcriptional start sites. We also identified approximately 8000 CpG islands with variable intermediate DNA methylation that seems to occur as a result of stochastic de novo methylation. Conclusion: WGBS provides an unbiased view and novel insights into the DNA methylome of ALL cells.
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| 29. |
- Farkas, Sanja A., 1983-, et al.
(författare)
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DNA methylation changes in genes frequently mutated in sporadic colorectal cancer and in the DNA repair and Wnt/beta-catenin signaling pathway genes
- 2014
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Ingår i: Epigenomics. - : Future Medicine. - 1750-1911. ; 6:2, s. 179-191
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The onset and progression of colorectal cancer (CRC) involves a cascade of genetic and/or epigenetic events. The aim of the present study was to address the DNA methylation status of genes relevant in colorectal carcinogenesis and its progression, such as genes frequently mutated in CRC, genes involved in the DNA repair and Wnt signaling pathway.Material & methods: We analyzed methylation status in totally 160 genes in 12 paired colorectal tumors and adjacent healthy mucosal tissues using the Illumina Infinium Human Methylation 450 BeadChip.Results: We found significantly aberrant methylation in 23 genes (NEIL1, NEIL3, DCLRE1C, NHEJ1, GTF2H5, CCNH, CTNNB1, DKK2, DKK3, FZD5 LRP5, TLE3, WNT2, WNT3A, WNT6, TCF7L1, CASP8, EDNRB1, GPC6, KIAA1804, MYO1B, SMAD2 and TTN). External validation by mRNA expression showed a good agreement between hypermethylation in cancer and down-regulated mRNA expression of the genes EDNRB1, GPC6 and SMAD2, and between hypomethylation and up-regulated mRNA expression of the CASP8 and DCLRE1C genes.Conclusion: Aberrant methylation of the DCLRE1C and GPC6 genes are presented here for the first time and are therefore of special interest for further validation as novel candidate biomarker genes in CRC, and merit further validation with specific assays.
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| 30. |
- Sinha, Indranil, et al.
(författare)
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Genome-wide mapping of histone modifications and mass spectrometry reveal H4 acetylation bias and H3K36 methylation at gene promoters in fission yeast
- 2010
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Ingår i: Epigenomics. - 1750-1911. ; 2:3, s. 377-393
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Tidskriftsartikel (refereegranskat)abstract
- To map histone modifications with unprecedented resolution both globally and locus-specifically, and to link modification patterns to gene expression. Materials & methods: Using correlations between quantitative mass spectrometry and chromatin immunoprecipitation/microarray analyses, we have mapped histone post-translational modifications in fission yeast (Schizosaccharomyces pombe). Results: Acetylations at lysine 9, 18 and 27 of histone H3 give the best positive correlations with gene expression in this organism. Using clustering analysis and gene ontology search tools, we identified promoter histone modification patterns that characterize several classes of gene function. For example, gene promoters of genes involved in cytokinesis have high H3K36me2 and low H3K4me2, whereas the converse pattern is found ar promoters of gene involved in positive regulation of the cell cycle. We detected acetylation of H4 preferentially at lysine 16 followed by lysine 12, 8 and 5. Our analysis shows that this H4 acetylation bias in the coding regions is dependent upon gene length and linked to gene expression. Our analysis also reveals a role for H3K36 methylation at gene promoters where it functions in a crosstalk between the histone methyltransferase Set2(KMT3) and the histone deacetylase Clr6, which removes H3K27ac leading to repression of transcription. Conclusion: Histone modification patterns could be linked to gene expression in fission yeast.
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| 31. |
- Malmström Rognes, Åsa
(författare)
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The Evolution of Capital Adequacy Rules : the contrasting cases of Sweden and Britain
- 2022
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Ingår i: Scandinavian Economic History Review. - Abingdon : Taylor & Francis Group. - 0358-5522 .- 1750-2837. ; 70:1, s. 19-32
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Tidskriftsartikel (refereegranskat)abstract
- The regulation of bank capital has evolved from minimum capital requirements for joint-stock banks to elaborate risk-based capital adequacy rules. How did these regulations come about? How and why have they changed over time in different coutnries? Sweden began to regulate minimum capital in the nineteenth century. In 1911 an early version of capital adequacy was introduced. In addition to stringent regulation a separate inspection agency was given wide-ranging powers to ensure compliance. Britain also had minimum capital rules in place but during the twentieth century these two countries followed different paths in regulation and supervision of capital rules. This paper examines the Swedish case in detail and contrasts that with the British case. It is suggested that their respective civil and common law traditions may explain the divergent approaches to defining and regulating capital adequacy.
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