Methylation disorder in CLL
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Dan Landau
PROVIDER: E-GEOD-58889 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:DNA methylation profiling using RRBS in wild type and Dppa3 knockout ESCs.
2020-09-30 | E-MTAB-6800 | biostudies-arrayexpress
Project description:Purpose: The goal of this study was to compare the genome-wide promoter methylation alterations in macrophages and endothelial cells during hindlimb ischemia among normal, hyperlipidemic and type-2 diabetic mice. Methods: Unilateral hindlimb ischemia was induced by ligating femoral artery proximal to the bifurcation of superficial and deep femoral artery in mice deficient of LDL receptor and expressing only apolipoprotein B100 (LDLR-/-ApoB100/100, C57BL/6J background) (The Jackson Laboratory, Bar Harbor,USA) and mice with β-cell specific over-expression of insulin-like growth factor-2 in atherosclerotic background (IGF-II/LDLR-/-ApoB100/100, C57BL/6J background) with type 2 diabetic features on high-fat diet (TD 88173, Harlan Teklad: 42% of calories from fat and 0.15% from cholesterol, no sodium cholate) 8 weeks prior to surgery and continued throughout the study 1. C57BL/6J (WT) mice fed with regular chow-diet (R36, Lactamin) served as controls. All animals were aged between 20 to 24 weeks at the time of hindlimb operations. For sorting macrophages from ischemic muscles, ischemic gastrocnemius muscles were minced and enzymatically dissociated using a cocktail containing 450 U/mL Collagenase I, 125 U/mL Collagenase XI, 60 U/mL DNAseI, and 60 U/mL hyaluronidase (Sigma Aldrich) for 1 h at 37°C. The cells were then counted and divided into CD31+ve and CD31-vefractions using CD31 magnetic bead enrichment (Miltenyi Biotec). For macrophage sorting CD31-ve fraction was incubated for 15 minutes with rat anti-mouse CD16/32 mAb (Fc Block, BD-pharmingen) and stained with FITC conjugated rat anti-mouse F4/80 antibody (Serotec) for 20 minutes at 4ËC. For endothelial sorting CD31+ fraction was incubated for 15 minutes with rat anti-mouse CD16/32 mAb (Fc Block, BD-pharmingen) and stained with APC conjugated rat anti-mouse CD31 antibody (BD-pharmingen) and FITC conjugated rat anti-mouse CD45 ((BD-pharmingen) for 20 minutes at 4ËC. FACS sorting was performed on FACS AriaIII (BD Biosciences). Genomic DNA was isolated from FACS sorted macrophages and endothelial cells using AllPrep DNA/RNA/Protein Mini Kit (Qiagen Finland, Helsinki, Finland) according to manufacturer's instructions. Results: The sample similarity as assessed by Pearsonâs correlation matrix and Hierarchial clustering showed high correalation among macrophages, as well as endothelial cells. There was a clear clustering of macrophages and endothelial cells as evidence by their CpG methylation clustering, furthermore macrophages from HL and T2DM mice showed clear clustering compared to control macrophages. Differential methylation analysis of RRBS methylation data from macrophages and endothelial cells was performed using Methylkit. Using a threshold of adjusted p value (Q) <0.05 and percentage methylation difference of >5%, we identified 198 and 272 genes whose promoters were hypomethylated in HL and T2DM macrophages. Similarly, there were 102 and 136 gene promoters were hypermethylated in HL and T2DM macrophages, respectively compare to control macrophages. Thus, proximal promoter methylation suggested that HL and T2DM have convergent influences on the proximal promoter methylation of numerous macrophage specific genes. In order to find out whether these genes with differential methylated promoters were differentially expressed at mRNA expression level in purified macrophages, we further compared our data with the GEO datasets as above. Of the 198 genes with promoter hypomethylation in HL macrophages 72 genes were suggested to be upregulated in M1- MÏs; whereas, of the 102 genes with promoter hypermethylation, 51 genes were suggested to be upregulated in M2- MÏs. Similarly, out of 272 genes with differentially methylated promoters in T2DM macrophages 88 genes were suggested to be upregulated in M1-MÏs; whereas, out of 136 genes with promoter hypermethylation 60 genes were suggested to be upregulated in M2- MÏs. Thus a significant promoter hypomethylation of M1-MÏ and hypermethylation of M2-MÏ genes suggested the predominance of proinflammatory M1-MÏs in ischemic muscles of HL and T2DM compared to M2-MÏs in control mice. Conclusions: We found significant promoter hypomethylation of genes typical for proinflammatory M1-MÏs and hypermethylation of anti-inflammatory, proangiogenic M2-MÏ associated genes in HL and T2DM ischemic muscles. Epigenetic alterations skewing MÏ phenotype towards proinflammatory as opposed to anti-inflammatory, proangiogenic and tissue repair phenotype may contribute to impaired adaptive vascular growth in these pathological conditions. Macrophages and endothelial whole genome DNA methylation was performed in triplicates (Each sample was pooled from 3-4 mice) by RRBS Sequencing approach using Illumina HiSeq 2500. qRTâPCR validation was performed using TaqMan assays.
2015-12-21 | E-GEOD-65759 | biostudies-arrayexpress
Project description:DNA methylation profiling by reduced representation bisulfite sequencing of PAF15KRKR and wild type mouse embryonic stem cells
2020-01-28 | E-MTAB-7930 | biostudies-arrayexpress
Project description:Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity.  Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure, and offers  insight into how obesity may propagate metabolic dysfunction to the next generation. Examination of the DNA methylation status, histone retention and sncRNA expression of the semen of 13 lean and 10 obese individuals; as well as the DNA methylation status of the semen of 6 obese men undergoing Roux-en-Y GBP surgery, at three time points: approximately 1 week before, 1 week after and 1 year after the surgery.
2015-12-04 | E-GEOD-74426 | biostudies-arrayexpress
Project description:Migration is essential for the reproduction and survival of many animals, yet little is understood about its underlying molecular mechanisms. We used the salmonid Oncorhynchus mykiss to gain mechanistic insight into smoltification, which is a morphological, physiological, and behavioral transition undertaken by some juveniles that culminates in a seaward migration. This species is experimentally tractable and, unlike common model species, displays intra- and inter-population variation in migration propensity. Migratory individuals can produce non-migratory progeny and vice versa, indicating a high degree of phenotypic plasticity. One potential way that phenotypic plasticity might be linked to variation in migration-related life history tactics is through epigenetic regulation of gene expression. To explore this, we quantitatively measured genome-scale DNA methylation in fin tissue using reduced representation bisulfite sequencing of F2 siblings produced from a cross between steelhead (migratory) and rainbow trout (non-migratory) lines. We identified 57 differentially methylated regions (DMRs) between smolt and resident O. mykiss juveniles. DMRs were of high magnitude, ranging from 20-62% differential methylation between life history types, and over half of the gene-associated DMRs were in transcriptional regulatory regions. Many of the DMRs encode proteins with activity relevant to migration-related transitions (e.g. circadian rhythm pathway, nervous system development, protein kinase activity). This study provides the first evidence of a relationship between epigenetic variation and life history divergence associated with a migration-related transition in any species. Comparing global DNA methyldation profiles (via RRBS) of resident and smolt O. mykiss siblings using caudal fin tissue.
2015-06-18 | E-GEOD-62195 | biostudies-arrayexpress
Project description:The samples were collected from the participants of the Finnish Diabetes Prediction and Prevention (DIPP) Study, born between 1995 and 2006. DIPP is a prospective follow-up cohort of children with a moderate or high risk of type 1 diabetes, based on the HLA-DR-DQ genotype. Islet cell autoantibodies (ICA, GADA, IAA, IA2A and ZnT8A) were measured 1 - 4 times per year until age 15 or year 2018. The aim was to study associations between perinatal DNA methylation marks and later progression to type 1 diabetes. Case individuals who became persistently positive for at least two biochemical autoantibodies (GADA, IAA, IA2A or ZnT8A) and/or were diagnosed with type 1 diabetes during the follow-up were compared to the control individuals who remained autoantibody-negative throughout the follow-up. These data were also used in the development of data analysis methodology in bisulfite sequencing studies. To protect the privacy of the study participants, the sequence read data are not publicly available. However, the processed data can be downloaded here. These include two count matrices: \\"methylated_reads\\" and \\"total_reads\\". The matrix \\"methylated_reads\\" contains methylated read counts at each high-coverage CpG site (altogether approximately 2.5 million rows) at each of the 173 samples (173 columns), and the matrix \\"total_reads\\" contains the corresponding total read counts (coverage). Please notice that the methylated read counts are read counts, not percentages. Methylation proportions can be calculated as methylated_reads/total_reads. The row names are the genomic locations of these CpG sites in hg19 (GRCh37) coordinates (1,2). For privacy reasons, all potential SNPs were excluded from these publicly available count matrices. Specifically, we removed all common (minor allele frequency > 1 %) human SNPs, as listed in dbSNP (3). We also removed all SNPs that were detected in one or more samples even with \\"low\\" evidence by BS-SNPer, which is a software for detecting SNPs from bisulfite sequencing data (4). Altogether 204443 out of 2752981 rows were removed from the original coverage-filtered count matrices that were analyzed in the present study. Description of the sample attributes: Individual: The individual-specific identifiers, such as “Subject1”. Since each sample is from a different individual, these correspond to the sample identifiers (Subject1 == Sample 1 etc.) Experimental Group: The variable of interest (called \\"class\\" in the associated publications) with three possible values: 1) case, 2) control and 3) NA (neither case nor control). 1) Case: became persistently positive for at least two biochemical autoantibodies (GADA, IAA, IA2A or ZnT8A) and/or diagnosed with type 1 diabetes during the follow-up. 2) Control: remained autoantibody-negative throughout the follow-up. 3) NA: The remaining 51 individuals with a missing value (“NA”) did not qualify as cases or controls, since they were either persistently positive for only 1 biochemical autoantibody or transiently positive for one or more autoantibodies. We excluded these 51 individuals from the case-control-comparison but included them in the comparison between the sexes. Library preparation batch: The sequencing libraries were prepared in 7 batches. The names of the batches do not have any special meaning. That is, \\"1A\\" is not necessarily more similar to \\"1B\\" than it is to \\"3B\\". We treated this as a categorical technical variable with 7 categories. PC1 and PC2: Projections of the sample-specific methylation proportion vectors on the first two orthonormal principal components. The principal component analysis (PCA) was performed on the original coverage-filtered methylation proportion matrix (methylated/total reads), where missing values at each CpG site were imputed by the median over samples with non-missing values. The original methylation proportion matrix included 2752981 rows, whereas these publicly available matrices include 2548538 rows (all potential SNPs excluded). Hence, PCA on the publicly available data would result in slightly different values for PC1 and PC2. We included these as covariates in the differential methylation analysis to represent technical variation (in addition to the library preparation batches). References 1. Church DM, Schneider VA, Graves T, Auger K, Cunningham F, Bouk N, et al. Modernizing reference genome assemblies. PLoS Biol. 2011 Jul;9(7):e1001091. 2. Genome Reference Consortium. NCBI downloads: https://hgdownload.soe.ucsc.edu/goldenPath/hg19/bigZips/hg19.fa.gz, accessed Feb 10th, 2019 3. NCBI. dbSNP: https://ftp.ncbi.nih.gov/snp/organisms/human_9606_b151_GRCh37p13/VCF/common_all_20180423.vcf.gz, accessed April 29th, 2021 4. Gao S, Zou D, Mao L, Liu H, Song P, Chen Y, et al. BS-SNPer: SNP calling in bisulfite-seq data. Bioinformatics. 2015 Dec 15;31(24):4006–8.
2022-06-06 | E-MTAB-10530 | biostudies-arrayexpress
Project description:Tet-mediated DNA oxidation is a new type of epigenetic modification in mammals and its role in the regulation of cell fate transition remains poorly understood. Here, we derive mouse embryonic fibroblasts (MEFs) deleted in all three Tet genes and examine their capability to be reprogrammed into iPS cells. We demonstrate that these Tet-deficient MEFs cannot be reprogrammed due to a blockage in the mesenchymal-to-epithelial transition (MET). Reprogramming of MEFs deficient in TDG is similarly blocked. The blockage is caused by impaired activation of crucial microRNAs, which depends on oxidative demethylation promoted by Tet and TDG. Reintroduction of either miR-200c or catalytically active Tet and TDG restores reprogramming to the respective knockout MEFs. Thus, oxidative demethylation is essential for somatic cell reprogramming. These findings provide mechanistic insights into the operation of epigenetic barriers in cell lineage conversion. Reduced Representation Bisulfite (RRBS, MspI,~75-400bp size fraction) and Tet-Assisted RRBS (TARRBS) of MEFs & reprogramming MEFs at Day 5
2014-02-19 | E-GEOD-52741 | biostudies-arrayexpress
Project description:We report the analysis of DNA methylation in mouse chromaffin cell lines using reduced representation bisulfite sequencing (RRBS). We compared DNA methylation profiles of cell lines with or without a knock-out of Sdhb gene, showing that Sdhb disruption results in a hypermethylator phenotype. Reduced representation bisulfite sequencing of 4 mouse chromaffin cell samples (2 Sdhb wild-type and 2 Sdhb knock-out).
2013-05-06 | E-GEOD-44350 | biostudies-arrayexpress
Project description:Mammary gland development and luminal differentiation occur largely postnatally during puberty and pregnancy. We found that pregnancy had the most significant effects on stem cells, inducing a distinct epigenetic state that remained stable through life. Mammary glands were collected from mice at non-pregnant and pregnant stages for DNA extraction and DNA methylation analysis via mRRBS (multiplexed reduced representation bisulfite sequencing).
2015-01-22 | E-GEOD-54149 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-05-06 | E-GEOD-43298 | biostudies-arrayexpress