5-Hydroxymethylcytosine profiling of aging hippocampi
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE102473 | GEO | 2018/02/25
REPOSITORIES: GEO
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Project description:We present a long-read, single-molecule mapping technology that generates hybrid genetic/epigenetic profiles of native chromosomal DNA. The genome-wide distribution of 5-hmC in human peripheral blood cells correlates well with 5-hmC DNA immunoprecipitation (hMeDIP) sequencing. However, the long single-molecule read-length of 100 kbp-1 Mbp produces 5-hmC profiles across variable genomic regions that failed to show up in the sequencing data. In addition, optical 5-hmC mapping shows a strong correlation between the 5-hmC density in gene bodies and the corresponding level of gene expression.
2018-06-08 | GSE115454 | GEO
Project description:The discovery of cytosine hydroxymethylation (5-hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behavior in colon cancer. 5-hmC is globally reduced in proliferating cells such as colon tumors and the gut crypt progenitors, from which tumors can arise. Here, we show that colorectal tumors and cancer cells express Ten-Eleven Translocation (TET) transcripts at levels similar to normal tissues. Genome-wide analyses show that promoters marked by 5-hmC in normal tissue, and those identified as TET2 targets in colorectal cancer cells, are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer cells confirm that these promoters are resistant to methylation gain independently of sustained TET2 expression. We also find that a considerable number of the methylation gain-resistant promoters marked by 5-hmC in normal colon overlap with those that are marked with poised bivalent histone modifications in embryonic stem cells. Together our results indicate that promoters that acquire 5-hmC upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5-hmC in tumors. Our study highlights the potential of cytosine modifications as biomarkers of cancerous cell proliferation. 5 normal colon samples and 4 matching tumor samples were profiled for 5-hydroxymethylcytosine content genomewide using hmeDIP-seq. The colorectal cancer cell line HCT116 was profiled for binding of TET2 genomewide by chromatin immunoprecipitation sequencing (ChIP-seq).
2015-02-03 | E-GEOD-47590 | biostudies-arrayexpress
Project description:5-Hydroxymethylcytosine (hmC) is particularly abundant in mammalian brains with yetto be revealed functions. Here, we present genome-wide and single-base-resolutionmaps of hmC and mC in the human brain. We demonstrated that hmCs increasemarkedly from the fetal to the adult stage, and in the adult brain, 13.4% of all CpGs arehighly hydroxymethylated with strong enrichment at genic regions and distal regulatoryelements. Notably, hmC peaks were identified at the 5' splicing sites at the exon-intronboundary, suggesting a mechanistic link between hmC and splicing. We also report asurprising transcription-correlated hmC bias toward the sense strand and an mC biastoward the antisense strand of gene bodies. Furthermore, hmC is negatively correlatedwith H3K27me3-marked repressive genomic regions, and is more enriched in poisedenhancers than active enhancers. Our results provide insights into understanding themultiple potential functions of hmC in the human brain. A cell type specific hydroxymethylome sample of NeuN+ neurons in frontal lobe from the same adult individual, whose TAB-Seq data was deposited in GSE46710
2014-02-22 | E-GEOD-55249 | biostudies-arrayexpress
Project description:5-Hydroxymethylcytosine (hmC) is particularly abundant in mammalian brains with yetto be revealed functions. Here, we present genome-wide and single-base-resolutionmaps of hmC and mC in the human brain. We demonstrated that hmCs increasemarkedly from the fetal to the adult stage, and in the adult brain, 13.4% of all CpGs arehighly hydroxymethylated with strong enrichment at genic regions and distal regulatoryelements. Notably, hmC peaks were identified at the 5' splicing sites at the exon-intronboundary, suggesting a mechanistic link between hmC and splicing. We also report asurprising transcription-correlated hmC bias toward the sense strand and an mC biastoward the antisense strand of gene bodies. Furthermore, hmC is negatively correlatedwith H3K27me3-marked repressive genomic regions, and is more enriched in poisedenhancers than active enhancers. Our results provide insights into understanding themultiple potential functions of hmC in the human brain.
2014-02-22 | GSE55249 | GEO
Project description:Single cell RNAseq of Old (19 month) and Young (3 month) mouse brain endothelial cells isolated from hippocampi of C57BL6 males.
2019-03-07 | GSE127963 | GEO
Project description:DNA hydroxymethylation (5hmC) represents a new layer of epigenetic regulation in addition to DNA methylation (5mC). The genome-wide patterns of 5hmC distribution in many tissues and cells have recently been revealed by hydroxymethylated DNA immunoprecipitation (hMeDIP) followed by high throughput sequencing or tiling arrays. However, the DNA hydroxymethylome data generated by the conventional hMeDIP-seq method can not be used for direct quantitative comparison across different samples. In this study, we report a new quantitative hMeDIP-seq method, which uses barcode technology to label different DNA samples and performs hMeDIP-seq for multiple samples in one reaction system. Using this new method, we profiled and compared the DNA hydroxymethylomes of mouse ES cells (ESCs) and mouse ESCs-derived neural progenitor cells (NPCs). 5hmC levels around TSS in either ESCs or NPCs had negative correlation with gene expression levels，while 5hmC levels at gene body regions had different correlation with gene expression, depending on cell types. We identified differential hydroxymethylated regions (DHMRs) by comparing the 5hmC density of all 5hmC peaks between ESCs and NPCs. Many selected DHMRs (e.g., Ankrd23, Hist1h2aa, Fbxw7, and Epha2) were validated by hMeDIP-qPCR. Furthermore, we analyzed the relationship between the alteration of DNA hydroxymethylation and the gene expression change during neural differentiation, and our data suggest that both up- and down-regulated genes exhibited dramatic decrease in 5hmC during neural differentiation while the alteration of 5hmC had weak positive correlation with the changes in gene expression. Taken together, our data demonstrate that quantitative hMeDIP-seq is a powerful approach for genome-wide comparison of DNA hydroxymethylation across multiple samples. Importantly, the DHMRs between ESCs and NPCs uncovered in this study may provide clues for further investigation of the function of 5hmC in gene regulation and neural differentiation. Comparision of the genome-wide distribution of 5hmC in mouse embryonic stem cells and mouse ES-derived neural progenitor cells.
2013-03-08 | E-GEOD-40810 | biostudies-arrayexpress
Project description:DNA hydroxymethylation (5hmC) represents a new layer of epigenetic regulation in addition to DNA methylation (5mC). The genome-wide patterns of 5hmC distribution in many tissues and cells have recently been revealed by hydroxymethylated DNA immunoprecipitation (hMeDIP) followed by high throughput sequencing or tiling arrays. However, the DNA hydroxymethylome data generated by the conventional hMeDIP-seq method can not be used for direct quantitative comparison across different samples. In this study, we report a new quantitative hMeDIP-seq method, which uses barcode technology to label different DNA samples and performs hMeDIP-seq for multiple samples in one reaction system. Using this new method, we profiled and compared the DNA hydroxymethylomes of mouse ES cells (ESCs) and mouse ESCs-derived neural progenitor cells (NPCs). 5hmC levels around TSS in either ESCs or NPCs had negative correlation with gene expression levels，while 5hmC levels at gene body regions had different correlation with gene expression, depending on cell types. We identified differential hydroxymethylated regions (DHMRs) by comparing the 5hmC density of all 5hmC peaks between ESCs and NPCs. Many selected DHMRs (e.g., Ankrd23, Hist1h2aa, Fbxw7, and Epha2) were validated by hMeDIP-qPCR. Furthermore, we analyzed the relationship between the alteration of DNA hydroxymethylation and the gene expression change during neural differentiation, and our data suggest that both up- and down-regulated genes exhibited dramatic decrease in 5hmC during neural differentiation while the alteration of 5hmC had weak positive correlation with the changes in gene expression. Taken together, our data demonstrate that quantitative hMeDIP-seq is a powerful approach for genome-wide comparison of DNA hydroxymethylation across multiple samples. Importantly, the DHMRs between ESCs and NPCs uncovered in this study may provide clues for further investigation of the function of 5hmC in gene regulation and neural differentiation.
2013-03-08 | GSE40810 | GEO
Project description:The most widely utilized approaches for quantifying DNA methylation involve the treatment of genomic DNA with sodium bisulfite, although this method cannot distinguish between DNA methylation (5mC) and DNA hydroxymethylation (5hmC). Previous studies have shown that 5hmC is enriched in the brain, although little is known about its genomic distribution and how it differs between anatomical regions and individuals. In this study, we combined oxidative bisulfite (oxBS) treatment with the Illumina Infinium 450K BeadArray to quantify genome-wide patterns of 5hmC in two distinct anatomical regions of the brain (prefrontal cortex and cerebellum) dissected from multiple individuals. We identified 37,145 and 65,563 sites passing our threshold for detectable 5hmC in the prefrontal cortex and cerebellumm, respectively, with 23,445 loci common across both brain regions. Distinct patterns of 5hmC were identified in each brain region, with notable differences in the genomic location of the most hydroxymethylated loci between these brain regions. Tissue-specific patterns of 5hmC were subsequently confirmed in an independent set of prefrontal cortex and cerebellum samples. Our data are available as downloadable UCSC genome browser tracks (http://epigenetics.iop.kcl.ac.uk/HMC/) as a resource to the community. Our study represents the first systematic analysis of 5hmC in the human brain, identifying tissue-specific hydroxymethylated positions and genomic regions characterized by inter-individual variation in DNA hydroxymethylation. This study demonstrates the utility of combining oxBS-treatment with the Illumina 450k methylation array to systematically quantify 5hmC across the genome and the potential utility of this approach for epigenomic studies of brain disorders.
2015-11-30 | GSE74368 | GEO
Project description:RNA was extracted from microdissected hippocampi from 10-month old DMSO or SCDi (Cayman 10566) ICV treated WT or 3xTg-AD mice.
2022-02-25 | GSE189693 | GEO
Project description:We investigated genome-wide analysis of 5-hydroxymethylcytosine (5hmC) distribution in mouse intestinal stem and differentiated cells using hydroxyMethylated DNA immunoprecipitation (hMeDIP) followed by sequencing. Genomic DNA from mouse intestinal stem (Lgr5+) and villus differentiated cells were sonicated, immunoprecipitated by a 5hmC antibody, and sequenced in order to identify differential hydroxymethylated regions and genes.
2016-11-23 | E-MTAB-5202 | biostudies-arrayexpress