H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells

In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type–independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors

Profiling of oxBS-450K 5-hydroxymethylcytosine in human placenta and brain reveals enrichment at imprinted loci

<p>DNA methylation (5-methylcytosine, 5 mC) is involved in many cellular processes and is an epigenetic mechanism primarily associated with transcriptional repression. The recent discovery that 5 mC can be oxidized to 5-hydromethylcytosine (5hmC) by TET proteins has revealed the “sixth base” of DNA and provides additional complexity to what was originally thought to be a stable repressive mark. However, our knowledge of the genome-wide distribution of 5hmC in different tissues is currently limited. Here, we sought to define loci enriched for 5hmC in the placenta genome by combining oxidative bisulphite (oxBS) treatment with high-density Illumina Infinium HumanMethylation450 methylation arrays and to compare our results with those obtained in brain. Despite identifying over 17,000 high-confidence CpG sites with consistent 5hmC enrichment, the distribution of this modification in placenta is relatively sparse when compared to cerebellum and frontal cortex. Supported by validation using allelic T4 β-glucosyltransferase assays we identify 5hmC at numerous imprinted loci, often overlapping regions associated with parent-of-origin allelic 5 mC in both placenta and brain samples. Furthermore, we observe tissue-specific monoallelic enrichment of 5hmC overlapping large clusters of imprinted snoRNAs-miRNAs processed from long noncoding RNAs (lncRNAs) within the <i>DLK1-DIO3</i> cluster on chromosome 14 and <i>SNRPN-UBE3A</i> domain on chromosome 15. Enrichment is observed solely on the transcribed alleles suggesting 5hmC is positively associated with transcription at these loci. Our study provides an extensive description of the 5hmC/5 mC landscape in placenta with our data available at <a href="http://www.humanimprints.net" target="_blank">www.humanimprints.net</a>, which represents the most comprehensive resource for exploring the epigenetic profiles associated with human imprinted genes.</p

Additional file 1: of A new approach to epigenome-wide discovery of non-invasive methylation biomarkers for colorectal cancer screening in circulating cell-free DNA using pooled samples

Graphical description of the protocol for DNA sample pooling. aExpected DNA concentration of the pool was calculated as follows: limiting ng · n total volume of the pool $$\frac{\left(\mathrm{limiting}\ \mathrm{ng}\right)\cdotp n}{\left(\mathrm{total}\ \mathrm{volume}\ \mathrm{of}\ \mathrm{the}\ \mathrm{pool}\right)}$$ where n is the number of individuals included in each pool (10). (PDF 311 kb

Additional file 4: of Epigenetic modifications in KDM lysine demethylases associate with survival of early-stage NSCLC

Figure S2. Analysis work flow. Adenocarcinoma and squamous cell carcinoma samples from Harvard, Spain, Norway, and Sweden cohorts were used for the discovery phase of analysis. Data from The Cancer Genome Atlas (TCGA) were used for Validation. Ranger is a weighted version of random forest for controlling for the covariates including age, gender, smoking status, and histological stage. Variable importance score (VIS) was estimated for each CpG site and was ranked in descending order. CpG sites ranked in top 10% in both discovery and validation sets were selected for further evaluation by Cox regression. Multiple testing correction by false discovery rate (FDR) method was used if necessary. (PDF 357 kb

Additional file 1: of Epigenetic modifications in KDM lysine demethylases associate with survival of early-stage NSCLC

Figure S1. Quality control processes for DNA methylation chip data. Quality control measures and exclusion criteria as applied to Harvard, Spain, Norway, Sweden, and The Cancer Genome Atlas (TCGA) sample cohorts. (PDF 642 kb

Additional file 2: of Epigenetic modifications in KDM lysine demethylases associate with survival of early-stage NSCLC

Table S1. Annotation of CpG sites in KDM gene family. (PDF 677 kb

Additional file 3: of Epigenetic modifications in KDM lysine demethylases associate with survival of early-stage NSCLC

Table S2. Distributions of CpG sites in KDM genes. (PDF 153 kb