Global distribution of DNA hydroxymethylation and DNA methylation in chronic lymphocytic leukemia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE113386 | GEO | 2019/01/23
REPOSITORIES: GEO
Similar Datasets
Project description:Methylation at the 5-position of cytosine is a well-studied epigenetic pathway. In addition to 5-methylcytosine (5mC), substantial amounts of 5-hydroxymethylcytosine (5hmC) also referred to as the 6th DNA base, have been detected in certain tissues, most notably the brain. However, the genomic distribution of this cytosine modification is unknown. Here, we have developed an immunoprecipitation technique (5hmC-IP) to examine the occurrence of 5hmC in human DNA from brain frontal lobe tissue. The distribution of 5hmC was compared to that of 5mC. We show that 5hmC is more selectively targeted to genes than is 5mC. 5hmC is found at promoters and is particularly enriched in intragenic regions (gene bodies) but is largely absent from non-gene regions. 5hmC peaks at transcription start sites did not correlate with gene expression levels or H3K4me3 peaks. However, presence of 5hmC in gene bodies was more positively correlated with gene expression levels than was presence of 5mC. Promoters of testis-specific genes showed strong 5mC peaks in brain DNA but were almost completely devoid of 5hmC. Our data provide a first overview of the genomic distribution of 5hmC in human brain and will set the stage for further functional characterization of this novel DNA modification. Comparison between 5hmC and 5mC profiles
2011-03-01 | E-GEOD-27051 | biostudies-arrayexpress
Project description:Methylation at the 5-position of cytosine is a well-studied epigenetic pathway. In addition to 5-methylcytosine (5mC), substantial amounts of 5-hydroxymethylcytosine (5hmC) also referred to as the 6th DNA base, have been detected in certain tissues, most notably the brain. However, the genomic distribution of this cytosine modification is unknown. Here, we have developed an immunoprecipitation technique (5hmC-IP) to examine the occurrence of 5hmC in human DNA from brain frontal lobe tissue. The distribution of 5hmC was compared to that of 5mC. We show that 5hmC is more selectively targeted to genes than is 5mC. 5hmC is found at promoters and is particularly enriched in intragenic regions (gene bodies) but is largely absent from non-gene regions. 5hmC peaks at transcription start sites did not correlate with gene expression levels or H3K4me3 peaks. However, presence of 5hmC in gene bodies was more positively correlated with gene expression levels than was presence of 5mC. Promoters of testis-specific genes showed strong 5mC peaks in brain DNA but were almost completely devoid of 5hmC. Our data provide a first overview of the genomic distribution of 5hmC in human brain and will set the stage for further functional characterization of this novel DNA modification.
2011-03-01 | GSE27051 | GEO
Project description:Genomic imprinting is a important biological process, which leads to parental specific gene expressions. Improper gene imprinting results in several developmental abnormalities, cancer and other diseases. Studies in mice indicated genomic imprinting establishment relied on parental allele-specific DNA methylation during gametogenesis. Despite the fact that genomic imprinting is highly conserved in mammalian, the species specific pattern exists. Until now, except that of in mouse, informations about imprinting patterns is little, especially in primates. Through generation genome-wide 5mC and 5hmC profiles for two types of haploid genomes from rhesus monkeys, including parthenogenetic haploid ESCs ( PG ha ESCs) (derived from rhesus monkey parthenogenetic embryos) and sperms. We clearly characterized and distinguished methylome (5mC) from hydroxymethylome (5hmC)(which can not discriminate from methylome in traditional bisulfite (BS) sequencing) in haploid genomes. Based on these information, we determined distribution patterns of 5mC and 5hmC in ha ESCs and sperms. Interestingly, both 5hmC levels and distribution patterns were similar in ha ESCs and sperms, and 5hmC which is enriched in the regions with low 5mC frequency. Meanwhile through comparing DNA methylation and hydroxymethylation status between sperms and ha ESCs, we first provided a fundamental information of monkey imprinted differentially methylated regions (DMRs) distribution in monkey chromosomes. Second, we observed that DMRs did not overlap with hydroxymethylated regions (DMR or DhMR), suggesting that establishment of imprinted regions was not interfered by 5hmC. Our results demonstrate DNA methylation profiling of PG ha ESCs and sperms can be uesed as a powerful and effective method to map and characterize imprinted regions in non-human primates genome.
2016-12-08 | GSE75817 | GEO
Project description:DNA methylation at the 5-position of cytosine (5-mC) is a key epigenetic mark critical for varius biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the Ten-Eleven Translocation (TET) family of DNA hydroxylases. Here we report that "loss of 5-hmC" is an epigenetic hallmark of melanoma with diagonostic and prognostic implications. Genome-wide mapping of 5-hmC in nevi and melanomas for the first time revealed loss of 5-hmC landscape in the melanoma epigenome. Downregulation of Isocitrate Dehydrogenase 2 (IDH2) and TET family enzymes proved to be one of the mechanisms underlying the loss of 5-hmC during melanoma development, and rebuilding the 5-hmC landscape in the melanoma epigenome by reintroducing active TET2 or IDH2 suppressed melanoma growth and increased tumor-free survival. Thus, our study establishes that "loss of 5-hmC" is a new epigenetic hallmark of melanoma and links IDH and TET family enzymes-mediated 5-hmC putative tumor suppressor pathway to the suppression of melanoma progression. Determine the genome-wide distribution of 5mC and 5hmC in benign nevus tissue, melanoma tissue, A2058 MOCK cells (overexpressing empty vector), A2058 TET2 cells (overexpressing wild type human TET), and A2058 TET2M cells (overexpressing mutant human TET).
2012-09-18 | E-GEOD-38231 | biostudies-arrayexpress
Project description:Identification the genome-wide distribution of 5-hmC in WT-MSCs and Tet2-/--MSCs by Genome-wide 5hmc Profiling.
2018-02-13 | GSE100072 | GEO
Project description:Adipose tissue is important for systemic metabolic homeostasis in response to environmental changes, and adipogenesis involves dynamic transcriptional regulation. DNA methylation on cytosine (C) of CpG (5mC) is an abundant epigenetic modification that mediates genomic imprinting and regulates gene expression. TET family enzymes (TET1, TET2 and TET3) oxidize the 5mC in DNA to 5-hydroxylmethylcytosine (5hmC), which associates with transcriptional activation. Through a phenotypic screen, we found TET inhibition decreased adipocyte differentiation from mesenchymal stem cells (MSCs). Comparing with the undifferentiated MSCs, the differentiated adipocytes exhibited much higher levels of 5hmC and slightly increased 5fC and 5caC. Higher 5hmC associated with better differentiation at single cell level. TET1 is upregulated in differentiation and depletion of it significantly impaired the gain of 5hmC. Furthermore, Tet1 depletion significantly hampered the adipocyte differentiation in vitro and adipose tissue maintenance in vivo. Using RNA-seq, 5mC and 5hmC-DNA immunoprecipitation, we found that Tet1 knockout led to decreased expression of genes associated with lipid metabolism and fat cell differentiation. Genes with loss of 5mC or gain of 5hmC in adipocytes include Lipe, Bmp4 and Rxra etc. Rxra is one of the critical TET1 modulated genes for adipose development, as RXRα agonist partially rescued the inhibitory effect of Tet1 knockout. Together, TET1-mediated active DNA demethylation plays an important role in adipose tissue.
2021-06-30 | GSE144644 | GEO
Project description:Adipose tissue is important for systemic metabolic homeostasis in response to environmental changes, and adipogenesis involves dynamic transcriptional regulation. DNA methylation on cytosine (C) of CpG (5mC) is an abundant epigenetic modification that mediates genomic imprinting and regulates gene expression. TET family enzymes (TET1, TET2 and TET3) oxidize the 5mC in DNA to 5-hydroxylmethylcytosine (5hmC), which associates with transcriptional activation. Through a phenotypic screen, we found TET inhibition decreased adipocyte differentiation from mesenchymal stem cells (MSCs). Comparing with the undifferentiated MSCs, the differentiated adipocytes exhibited much higher levels of 5hmC and slightly increased 5fC and 5caC. Higher 5hmC associated with better differentiation at single cell level. TET1 is upregulated in differentiation and depletion of it significantly impaired the gain of 5hmC. Furthermore, Tet1 depletion significantly hampered the adipocyte differentiation in vitro and adipose tissue maintenance in vivo. Using RNA-seq, 5mC and 5hmC-DNA immunoprecipitation, we found that Tet1 knockout led to decreased expression of genes associated with lipid metabolism and fat cell differentiation. Genes with loss of 5mC or gain of 5hmC in adipocytes include Lipe, Bmp4 and Rxra etc. Rxra is one of the critical TET1 modulated genes for adipose development, as RXRα agonist partially rescued the inhibitory effect of Tet1 knockout. Together, TET1-mediated active DNA demethylation plays an important role in adipose tissue.
2021-06-30 | GSE144613 | GEO
Project description:Through parallel processing of genomic DNA with bisulfite and oxidative bisulfite treatments on Illumina 450K arrays we resolved both 5mC and 5hmC in glioblastoma tissues. We developed and applied a novel technique for estimating 5mC, 5hmC, and unmethylated proportions from array data to glioblastoma tissues and compare with normal brain tissue. Genomic distribution of 5hmC was associated with features of transcription despite the glioblastoma genome being relatively depleted of 5hmC. When integrating 5mC and 5hmC data using a Gaussian finite mixture model approach, we observed significant associations between 5hmC levels and gene-sets involved in immune and RNA regulatory processes. We also observed an enrichment of 5hmC in introns, enhancer regions, and genes that are actively transcribed in glioblastomas from TCGA. Significant differences in patient survival were observed among classes of 5hmC obtained from a recursively partitioned mixture model. Glioblastoma dervied (n=30) DNA was subjected to tandem bisulfite and oxidative bisulfite conversion with an input of 4ug per sample using the TrueMethyl® kit v.1.1 (Cambridge Epigenetix) protocol optimized for Illumina HumanMethylation450 arrays.
2016-08-22 | E-GEOD-73895 | biostudies-arrayexpress
Project description:Through parallel processing of genomic DNA with bisulfite and oxidative bisulfite treatments on Illumina 450K arrays we resolved both 5mC and 5hmC in glioblastoma tissues. We developed and applied a novel technique for estimating 5mC, 5hmC, and unmethylated proportions from array data to glioblastoma tissues and compare with normal brain tissue. Genomic distribution of 5hmC was associated with features of transcription despite the glioblastoma genome being relatively depleted of 5hmC. When integrating 5mC and 5hmC data using a Gaussian finite mixture model approach, we observed significant associations between 5hmC levels and gene-sets involved in immune and RNA regulatory processes. We also observed an enrichment of 5hmC in introns, enhancer regions, and genes that are actively transcribed in glioblastomas from TCGA. Significant differences in patient survival were observed among classes of 5hmC obtained from a recursively partitioned mixture model.
2016-08-22 | GSE73895 | GEO
Project description:DNA methylation of C5-cytosine (5mC) in the mammalian genome is a key epigenetic event that is critical for various cellular processes. However, how the genome-wide 5mC pattern is dynamically regulated remains a fundamental question in epigenetic biology. The TET family of 5mC hydroxylases, which convert 5mC to 5-hydroxymethylcytosine (5hmC), have provided a new potential mechanism for the dynamic regulation of DNA methylation. The extent to which individual Tet family members contribute to the genome-wide 5mC and 5hmC patterns and associated gene network remains largely unknown. Here we report genome-wide mapping of Tet1 and 5hmC in mESCs and reveal a mechanism of action by which Tet1 controls 5hmC and 5mC levels in mESCs. In combination with microarray and mRNA-seq expression profiling, we identify a comprehensive yet intricate gene network influenced by Tet1. We propose a model whereby Tet1 controls DNA methylation both by binding to CpG-rich regions to prevent unwanted DNA methyltransferase activity, and by converting the existing 5mC to 5hmC through its enzymatic activity. This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 target loci, thereby providing a new regulatory mechanism for establishing the epigenetic landscape of mESCs, which ultimately contributes to mESC differentiation and the onset of embryonic development. To determine the genome-wide distribution of Tet1 and 5hmC in mouse ES cells, as well as identify the gene transcription changes after Tet1 depletion. GSM706669-GSM706671: We used GST pull-down followed by deep sequencing to map the DNA bound by the Tet1 CXXC domain in vitro. We made two mutants that have a single point mutation (Cys574 to Ala or Cys586 to Ala) in the core CXXC domain to ascertain the essential role of the CXXC domain in DNA binding by comparing the sequencing profile of DNA bound by wild type CXXC with the profiles of the CXXC mutants. GSM706672-GSM706673: Tet1 ChIP-seq was performed to identify the genome-wide distribution of Tet1 in mouse ES cells. GSM706674-GSM706679: We performed hydroxymethylated DNA immunoprecipitation (hMeDIP)-seq combined with a shRNA-mediated gene depletion strategy. To identify the loci specific 5hmC regulation by Tet1, we compared the 5hmC genome-wide distributions in control (Luc shRNA) and Tet1-depleted (Tet1 shRNA2863) mouse ES cells. GSM706680-GSM706682: To identify the gene regulation network by Tet1, we compared the gene expression profiles of control (scramble shRNA) and Tet1-depleted (Tet1 shRNA 2863 and Tet1 shRNA 3387) mouse ES cells determined by mRNA-seq.
2011-04-21 | E-GEOD-28532 | biostudies-arrayexpress