Journal: Cells

Article Title: The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

doi: 10.3390/cells11030362

Figure Lengend Snippet: Schematic overview: Gene expression and DNA-methylation data of the prefrontal cortex have been analyzed as a function of age and compared with data taken from gliomas and brain disorders in order to study alterations of modes of (epi-)genomic regulation [ , , ].

Article Snippet: Microarray-derived DNA methylation data (Infinium HumanMethylation27 BeadChips) were taken from Numata et al. [ ] in units of beta values of ~27,000 CpG’s located in the range of −1500 bp to +500 bp around the transcription start sites of 13,540 genes, thus serving as markers for their promoter methylation.

Techniques: Expressing, DNA Methylation Assay

Journal: Cells

Article Title: The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

doi: 10.3390/cells11030362

Figure Lengend Snippet: DNA methylation characteristics of the human brain (prefrontal cortex). ( a ) The pairwise correlation map indicates a virtually binary pattern of the aging brain in terms of two major clusters referring to prenatal and early childhood and ages from late childhood to late adults. ( b ) Mean SOM portraits averaged over intervals of increasing age. ( c ) The sample similarity net reveals a virtually one-dimensional development of promoter methylation in the brain samples. ( d ) “Spot” clusters of co-methylated genes are summarized in the overview map. Overall five hyper-methylation spots were detected (“A m ”–“E m ”). Upon aging hyper-methylation spots activate in a clockwise direction as indicated by the arrow. ( e ) The spot profiles reveal specific hyper- and hypo-methylation in different age intervals. Δm is the centralized log-ratio of methylated-versus-non-methylated CpGs in the gene promoters . ( f ) Methylation profiles and gene maps of aging gene sets taken from [ , , ] show decaying and increasing methylation levels as expected. The respective genes accumulate in map areas referring to spots A m and E m . ( g ) Boxplots of different methylation measures as a function of the age strata. The absolute methylation level continuously increases with age. The color code for the aging groups is used throughout the paper.

Article Snippet: Microarray-derived DNA methylation data (Infinium HumanMethylation27 BeadChips) were taken from Numata et al. [ ] in units of beta values of ~27,000 CpG’s located in the range of −1500 bp to +500 bp around the transcription start sites of 13,540 genes, thus serving as markers for their promoter methylation.

Techniques: DNA Methylation Assay, Methylation

Journal: Cells

Article Title: The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

doi: 10.3390/cells11030362

Figure Lengend Snippet: Gene function, expression, and methylation: ( a ) Gene expression and DNA promoter methylation of gene sets of the GO-category biological function (BP) provide an overview of functional changes upon aging. Expression and methylation were addressed independently. ( b ) Joint gene set analysis of gene expression and methylation as a function of age. Affected functions roughly divide into three major categories as indicated at the left axis of the heatmap. ( c ) Expression (E) versus methylation (M) plots of the three categories. Dots are mean values over all gene sets per category. Arrows serve as a guide for the eye and illustrate alterations upon aging. Anti-correlated relations between M and E suggest mutual repression while positive correlation can be rationalized in terms of repressive complexes (RC) which mediate interactions between M and E.

Article Snippet: Microarray-derived DNA methylation data (Infinium HumanMethylation27 BeadChips) were taken from Numata et al. [ ] in units of beta values of ~27,000 CpG’s located in the range of −1500 bp to +500 bp around the transcription start sites of 13,540 genes, thus serving as markers for their promoter methylation.

Techniques: Expressing, Methylation, Functional Assay

Journal: Cells

Article Title: The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

doi: 10.3390/cells11030362

Figure Lengend Snippet: Telomerase (TEL) and alternative (ALT) telomere maintenance (TM) related pathway activities taken from . The heatmap illustrates heterogeneous expression changes with age of genes taken from different branches of the TM pathways. Expression and methylation profiles of part of the processes and their bi-plot are shown in the right part of the figure. Expression of most ALT-related processes (except HR1 and HR2) decay with age while the TEL-related processes DKC1 and TEL increases. DNA virtually changes in an anticorrelated fashion.

Article Snippet: Microarray-derived DNA methylation data (Infinium HumanMethylation27 BeadChips) were taken from Numata et al. [ ] in units of beta values of ~27,000 CpG’s located in the range of −1500 bp to +500 bp around the transcription start sites of 13,540 genes, thus serving as markers for their promoter methylation.

Techniques: Expressing, Methylation

Journal: Cells

Article Title: The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

doi: 10.3390/cells11030362

Figure Lengend Snippet: Aging profiles of gene expression of a series of enzymes acting as writers or erasers of methylation marks at DNA and histone side chains. ( a ) Schematic sketch of the joint effect of histone lysine side chain and DNA methylation on the transcription of downstream genes and their relation to different chromatin states. ( b ) The overview heatmap shows that most of the genes, among them the DNA methyltransferases DNMT1 and DNMT3A,B and the demethylases Tet1–Tet3 (acting along the cytosine oxidation cycle) show large expression in babies and young children, which then decays with age, while another, smaller group gains expression upon aging, among them the H3K27me3 writing and chromatin compacting enzyme G9a (KMT1c). ( c ) Boxplots of the aging profiles of part of the enzymes reveal a variety of courses either increasing or decreasing with age. The different marks can have activating (e.g., triple methylation of lysine side chain H3K4 or H3K36), repressing (e.g., triple methylation at H3K27 or at H3K9) or poising (combination of H3K4 and H3K27) and chromatin compacting (H3K27 and H3K9) effect on transcription of the associated gene as schematically illustrated in part c. Combination of H3K4me3 and H3K27me3 gives rise to poised (“ready to go” and/plastic state) transcription while combination of H3K27me3 and H3K9me3 leads to compacted chromatin. For a detailed description of the enzymes and the histone code, see [ , , , , ] and [ , , ] for mechanisms in brain development. Maps of the different enzyme classes in the expression landscape of the brain are shown in . DNA cytosine (CpG) methylation and de-methylation oxidation cycle are shown in part b.

Article Snippet: Microarray-derived DNA methylation data (Infinium HumanMethylation27 BeadChips) were taken from Numata et al. [ ] in units of beta values of ~27,000 CpG’s located in the range of −1500 bp to +500 bp around the transcription start sites of 13,540 genes, thus serving as markers for their promoter methylation.

Techniques: Expressing, Methylation, DNA Methylation Assay, CpG Methylation Assay

Journal: Cells

Article Title: The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

doi: 10.3390/cells11030362

Figure Lengend Snippet: Mapping of epigenetic modifiers into gene expression SOM (see also b). Methyltransferases (red frames) and demethylases (blue frames) for part of modifications accumulate in different regions of the map referring to their activation in different phases of lifetime. Particularly, H3K4me3 writers show often high expression in early and intermediate phases of lifetime possibly reflecting transcriptional activation of the associated genes. For writers of the repressive H3K27me3 marks this relation reverses, i.e., writers activate with delay to erasers. A similar but smaller delay is observed for writers of DNA methylation, which also associate with repression of gene expression. Hence, modifications activating transcription seem to precede repressive modifications for H3K4, H3K27, DNA and, to a lesser degree, H3K36. Note that SOM mapping of the respective genes reveals these subtle shifts not immediately evident from the aging profiles ( b,c).

Article Snippet: Microarray-derived DNA methylation data (Infinium HumanMethylation27 BeadChips) were taken from Numata et al. [ ] in units of beta values of ~27,000 CpG’s located in the range of −1500 bp to +500 bp around the transcription start sites of 13,540 genes, thus serving as markers for their promoter methylation.

Techniques: Expressing, Activation Assay, DNA Methylation Assay

Journal: Cells

Article Title: The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

doi: 10.3390/cells11030362

Figure Lengend Snippet: Gene expression ( a ) and DNA methylation ( b ) of chromatin states in the fetal and adult brain. “Overlap” genes do not change their state between fetal and adult brain. Chromatin states refer to active promoters (TssA), transcribed genes (Tx), weak active enhancer and enhancer-like states (Enh, EnhG, EnhP), zinc finger proteins (ZNF), quiescent (Quies), heterochromatin (Het), heterochromatin repeats (HetRpts), poised promoters (TssP), repressed polycomb states (RepPC, weak: RepPCWk) and were taken from . The profiles can be divided into three major groups, referring to repressed, active/poised genes and heterochromatin/enhancers. The boxplots in the right part of ( a , b ) show profiles of selected groups of chromatin states across the age strata in GSZ (gene set Z-) score. ( c ) Correlation plots between expression and methylation for selected chromatin states (columns) and brain developmental stages (rows) indicate changing slopes and directions of the trajectories. ( d ) Schematic illustration of the expression (red) and methylation (blue) profiles across age. The red arrows indicate expected (nominal) expression in the respective states, e.g., low expression in repressed and high expression in transcribed states. ( e ) Number of genes in the different states. The largest fraction of genes in the fetal brain only refer to active states (TssA) while genes in adult brain (only and overlap) are mostly found in the other states.

Article Snippet: Microarray-derived DNA methylation data (Infinium HumanMethylation27 BeadChips) were taken from Numata et al. [ ] in units of beta values of ~27,000 CpG’s located in the range of −1500 bp to +500 bp around the transcription start sites of 13,540 genes, thus serving as markers for their promoter methylation.

Techniques: Expressing, DNA Methylation Assay, Methylation

Journal: Cells

Article Title: The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

doi: 10.3390/cells11030362

Figure Lengend Snippet: Comparison of the aging methylomes of healthy brain and that of lower-grade glioma (LGG). ( a ) The pairwise correlation heatmap between the samples indicates a strong correlation between different LGG-methylation and aging groups (red), e.g., between M1 ( IDH -wt group) and the prenatal brain. The LGG methylation data were trained together with the healthy brain methylomes using exSOM transfer learning . ( b ) The river plot visualizes the distribution of LGG tumor methylomes of the different M-groups among the age groups. The SOM portraits of the LGG were obtained using exSOM method applied to the aging data. ( c ) Distribution of samples of the M-groups among the age groups (part above) and vice versa, of the age groups among the LGG-groups (part below). ( d ) Characteristics of the M(ethylation) subtypes regarding IDH mutation status, chromosomal aberrations (7+/10−: gains at chromosome 7 and losses at chromosome 10, 1p/19q cod: codeletion at chromosomes 1p and 19q), GCIMP type and characteristics (GBM: glioblastoma, MES: mesenchymal, PA: pilocytic astrozytoma, IDH-A: IDH mutated astrocytoma, IDH-O: IDH mutated oligodendroglioma). ( e ) Aging profiles of DNA methylation of genes hypermethylated in the GCIMP and CIMP colon cancer , of PRC2 targets and cycling genes , and of the integral expression of genes at chromosomes 7, 10, and 19 (for further glioma related signatures see ). ( f ) Schematic summary: Cancer is initiated by genetic lesions usually in later adulthood (>45 years). Developmental trajectories point towards induction of stemness-like cancer cells (M1 and partly M4), subsequent immuno-aging (M2, M3), or metabo-aging (M5) which resemble different ages of the healthy brain. Development of the IDH -mut gliomas is shaped by altered DNA methylation.

Article Snippet: Microarray-derived DNA methylation data (Infinium HumanMethylation27 BeadChips) were taken from Numata et al. [ ] in units of beta values of ~27,000 CpG’s located in the range of −1500 bp to +500 bp around the transcription start sites of 13,540 genes, thus serving as markers for their promoter methylation.

Techniques: Methylation, Mutagenesis, DNA Methylation Assay, Expressing

Journal: Cells

Article Title: The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

doi: 10.3390/cells11030362

Figure Lengend Snippet: Comparison of the aging transcriptome of healthy brain and that of lower-grade glioma (LGG). ( a ) The pairwise correlation heatmap between the samples indicates correlation between different LGG-methylation and aging groups (red), e.g., between E1, E2 and E6 and the newborn brain. ( b ) The river plot visualizes distribution of LGG tumor methylomes of the different E-groups among the age groups. The SOM portraits of the LGG were obtained using exSOM method applied to the aging data. ( c ) Distribution of samples of the E-groups among the age groups (part above) and vice versa, of the age groups among the LGG-groups (part below). ( d ) Characteristics of the E(xpression) subtypes regarding IDH mutation status, chromosomal aberrations (7+/10−gains at chromosome 7 and losses at chromosome 10, 1p/19q cod codeletion at chromosomes 1p and 19q). Comparison of the aging methylomes of healthy brain and that of lower-grade glioma (LGG). The pairwise correlation heatmap between the samples indicates strong correlation between different LGG-methylation and aging groups (red), e.g., between M1 ( IDH -wt group) and the prenatal brain. The LGG methylation data were trained together with the healthy brain methylomes using exSOM transfer learning . The river plot visualizes distribution of LGG tumor methylomes of the different M-groups among the age groups. The SOM portraits of the LGG were obtained using exSOM method applied to the aging data. Distribution of samples of the M-groups among the age groups (part above) and vice versa, of the age groups among the LGG-groups (part below). Characteristics of the M(ethylation) subtypes regarding IDH mutation status, chromosomal aberrations (7+/10−gains at chromosome 7 and losses at chromosome 10, 1p/19q cod codeletion at chromosomes 1p and 19q), GCIMP type and characteristics (GBM glioblastoma, MES mesenchymal, PA pilocytic astrocytoma, IDH-A IDH mutated astrocytoma, IDH-O IDH mutated oligodendroglioma). Aging profiles of DNA-methylation of genes hypermethylated in the GCIMP and CIMP colon cancer , of PRC2 targets and cycling genes and of the integral expression of genes at chromosomes 7, 10 and 19.

Article Snippet: Microarray-derived DNA methylation data (Infinium HumanMethylation27 BeadChips) were taken from Numata et al. [ ] in units of beta values of ~27,000 CpG’s located in the range of −1500 bp to +500 bp around the transcription start sites of 13,540 genes, thus serving as markers for their promoter methylation.

Techniques: Methylation, Mutagenesis, DNA Methylation Assay, Expressing

Journal: Cells

Article Title: The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

doi: 10.3390/cells11030362

Figure Lengend Snippet: Chromosomal gene expression and methylation: ( a ) Chromosomal expression partly show pronounced age courses, particularly of Chr. 10, Chr. 7 and Chr. 19. Aberrant copy numbers of these chromosomes govern gliomagenesis into different subtypes (see main text). ( b ) Changes in chromosomal DNA methylation are much less pronounced. ( c ) Methylation versus expression trajectories (see for method) reveal turns into different directions at a “breakpoint” in the adolescent–early adult age range. The different trajectories of Chr. 10 refer to genes located in spots D, E and F. The show similar courses in childhood but different courses mainly due to different expression changes in adulthood.

Article Snippet: Microarray-derived DNA methylation data (Infinium HumanMethylation27 BeadChips) were taken from Numata et al. [ ] in units of beta values of ~27,000 CpG’s located in the range of −1500 bp to +500 bp around the transcription start sites of 13,540 genes, thus serving as markers for their promoter methylation.

Techniques: Expressing, Methylation, DNA Methylation Assay

Journal: Cells

Article Title: The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

doi: 10.3390/cells11030362

Figure Lengend Snippet: Age profiles of gene expression and DNA methylation of G-protein coupled receptors ( GPCR ). ( a ) GPCR genes collected in the set Reactome GPCR signaling, ( b ) the set of GPCR genes showing pronounced differential methylation in LGG methylation groups (spot B’ in ), and ( c ) sets of GPCR differentially expressed (up or down) in patients of different psychic disorders compared with healthy controls taken from . The age ranges referring to the respective differential expression are marked by red marks.

Article Snippet: Microarray-derived DNA methylation data (Infinium HumanMethylation27 BeadChips) were taken from Numata et al. [ ] in units of beta values of ~27,000 CpG’s located in the range of −1500 bp to +500 bp around the transcription start sites of 13,540 genes, thus serving as markers for their promoter methylation.

Techniques: Expressing, DNA Methylation Assay, Methylation

Journal: Cells

Article Title: The Transcriptome and Methylome of the Developing and Aging Brain and Their Relations to Gliomas and Psychological Disorders

doi: 10.3390/cells11030362

Figure Lengend Snippet: Combined changes of DNA methylation, gene expression, and chromatin states relate to brain development and aging. DNA demethylation of restrictive chromatin and methylation of permissive chromatin activate/deactivate different cell functions with age in a mostly irreversible fashion. Differentiation of neuronal tissue proceeds in active states which then become stabilized after repression of developmental genes. Poised states maintain plasticity while PRC2-repressed states maintain cellular identity of differentiated neuronal tissue. In particular, transitions between the latter states are partly reversible due to (de-)methylation equilibria governed by the activity of methyl writing, erasing and reading enzymes, and a large battery of cofactors such as PRC2.

Article Snippet: Microarray-derived DNA methylation data (Infinium HumanMethylation27 BeadChips) were taken from Numata et al. [ ] in units of beta values of ~27,000 CpG’s located in the range of −1500 bp to +500 bp around the transcription start sites of 13,540 genes, thus serving as markers for their promoter methylation.

Techniques: DNA Methylation Assay, Expressing, Methylation, Activity Assay

Journal: International Journal of Molecular Sciences

Article Title: Effects and Mechanism of Particulate Matter on Tendon Healing Based on Integrated Analysis of DNA Methylation and RNA Sequencing Data in a Rat Model

doi: 10.3390/ijms23158170

Figure Lengend Snippet: ( A ) Kyoto Encyclopedia of Genes and Genome (KEGG) pathways associated with the significantly upregulated and downregulated differentially expressed genes (DEGs) between particulate matter (PM)-exposed and control (non-PM) rats ( p < 0.05). ( B ) Canonical pathways with significant Z-scores (>2) identified using ingenuity pathway analysis. Heatmaps showing the DEGs in the ( C ) cAMP response element-binding protein (CREB) and ( D ) cAMP signaling pathways. ( E ) Schematic diagram showing the methods and criteria for gene analysis. ( F ) Venn diagram showing the combined DNA methylation and transcriptome data. The red circle indicates 67 genes exhibiting hypomethylated/upregulated expression. ( G ) The top five KEGG pathways associated with the hypomethylated/upregulated genes.

Article Snippet: A DNA methylation microarray was performed by Genomictree (Daejeon, Korea) using the tendon tissues (n = 3 per group) and a custom-designed Agilent-based microarray platform with 2 × 400 K probes per slide (popular_2X400K_chip; Agilent Design ID: 086791; Agilent Technologies, Santa Clara, CA, USA).

Techniques: Control, Binding Assay, Protein-Protein interactions, DNA Methylation Assay, Expressing