Integrative "-Omics" Analysis in Primary Human Hepatocytes Unravels Persistent Mechanisms of Cyclosporine A-Induced Cholestasis
Wolters J.E. et al.
Cyclosporine A (CsA) is an undecapeptide with strong immunosuppressant activities and is used a lot after organ transplantation. Furthermore, it may induce cholestasis in the liver. In general, the drug-induced cholestasis (DIC) pathway includes genes involved in the uptake, synthesis, conjugation, and secretion of ...
Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity
Keller M. et al.
DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese vs. obese individ...
Novel regional age-associated DNA methylation changes within human common disease-associated loci
Bell CG et al.
Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional loci.
In a discovery set of 2238 peripheral-blood genome-wide DNA methylomes aged 1...
Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing
Amabile A. et al.
Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently...
Trichloroethylene-Induced DNA Methylation Changes in Male F344 Rat Liver
Jiang Y. et al.
Trichloroethylene (TCE), a common environmental contaminant, causes hepatocellular carcinoma in mice but not in rats. To understand the mechanisms of the species-specific hepatocarcinogenecity of TCE, we examined the methylation status of DNA in the liver of rats exposed to TCE at 0 or 1000 mg/kg b.w. for 5 days usi...
Dynamic Interplay between the Transcriptome and Methylome in Response to Oxidative and Alkylating Stress
Deferme L et al.
In recent years, it has been shown that free radicals not only react directly with DNA but also regulate epigenetic processes such as DNA methylation, which may be relevant within the context of, for example, tumorigenesis. However, how these free radicals impact the epigenome remains unclear. We therefore investiga...
Efficiency of methylated DNA immunoprecipitation bisulphite sequencing for whole-genome DNA methylation analysis
Jeong HM et al.
We compared four common methods for measuring DNA methylation levels and recommended the most efficient method in terms of cost and coverage.
MATERIALS & METHODS:
The DNA methylation status of liver and stomach tissues was profiled using four different methods, whole-genome bisulphite sequencing (WG-BS), targe...
Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma
Linda Rieswijka, Sandra M.H. Claessena, Otto Bekersc, Marcel van Herwijnena, Daniël H.J. Theunissena, Danyel G.J. Jennena, Theo M.C.M. de Koka, Jos C.S. Kleinjansa,Simone G.J. van Bredaa
Chronic exposure to aflatoxin B1 (AFB1) has, in certain regions in the world, been strongly associated with hepatocellular carcinoma (HCC) development. AFB1 is a very potent hepatotoxic and carcinogenic mycotoxin which is frequently reported as a food contaminant. Epigenetic modifications provoked by environmental e...
Paternal B Vitamin Intake Is a Determinant of Growth, Hepatic Lipid Metabolism and Intestinal Tumor Volume in Female Apc1638N Mouse Offspring
Sabet JA, Park LK, Iyer LK, Tai AK, Koh GY, Pfalzer AC, Parnell LD, Mason JB, Liu Z, Byun AJ, Crott JW
The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well.
In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intest...
Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through
Batista L et al.
The miR-200 family members have been implicated in stress responses and ovarian tumorigenesis. Here, we find that miR-200c/141 transcription is intimately linked to the transcription of the proximal upstream gene PTPN6 (SHP1) in all physiological conditions tested. PTPN6 and miR-200c/141 are transcriptionally co-reg...
Maternal immune activation induces GAD1 and GAD2 promoter remodeling in the offspring prefrontal cortex
Labouesse MA et al.
Maternal infection during pregnancy increases the risk of neurodevelopmental disorders in the offspring. In addition to its influence on other neuronal systems, this early-life environmental adversity has been shown to negatively affect cortical γ-aminobutyric acid (GABA) functions in adult life, including imp...
DNA methylation profiling: comparison of genome-wide sequencing methods and the Infinium Human Methylation 450 Bead Chip
Walker DL, Bhagwate AV, Baheti S, Smalley RL, Hilker CA, Sun Z, Cunningham JM
To compare the performance of four sequence-based and one microarray methods for DNA methylation profiling.
DNA from two cell lines were profiled by reduced representation bisulfite sequencing, methyl capture sequencing (SS-Meth Seq), NimbleGen SeqCapEpi CpGiant(Nimblegen MethSeq), methylated DNA...
High cortisol in 5-year-old children causes loss of DNA methylation in SINE retrotransposons: a possible role for ZNF263 in stress-related diseases
Nätt D, Johansson I, Faresjö T, Ludvigsson J, Thorsell A
Childhood stress leads to increased risk of many adult diseases, such as major depression and cardiovascular disease. Studies show that adults with experienced childhood stress have specific epigenetic changes, but to understand the pathways that lead to disease, we also need to study the epigenetic l...
Arterial endothelial methylome: differential DNA methylation in athero-susceptible disturbed flow regions in vivo
Jiang YZ1, Manduchi E2, Stoeckert CJ Jr3, Davies PF
Atherosclerosis is a heterogeneously distributed disease of arteries in which the endothelium plays an important central role. Spatial transcriptome profiling of endothelium in pre-lesional arteries has demonstrated differential phenotypes primed for athero-susceptibility at hemodynamic sites associat...