Trajectories of DNA hydroxymethylation across human brain development
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE94014 | GEO | 2017/08/25
SECONDARY ACCESSION(S): PRJNA369254
REPOSITORIES: GEO
Similar Datasets
Project description:Dynamic changes to the epigenome mediate key neurobiological and cognitive processes in the central nervous system, and also play a role in transcriptional regulation during brain development. Although the importance of DNA methylation in brain development is highlighted by the neurodevelopmental deficits associated with mutations in genes including methyl-CpG binding protein 2 (MECP2), our knowledge about the specific methylomic trajectories associated with human neurodevelopment is extremely limited. Here we report an analysis of genome-wide patterns of DNA methylation in 179 human fetal cortex samples. Bisulphite converted DNA from 179 human brain samples was hybridized to the Illumina 450K Human Methylation Beadchip.
2014-12-19 | E-GEOD-58885 | biostudies-arrayexpress
Project description:Dynamic changes to the epigenome mediate key neurobiological and cognitive processes in the central nervous system, and also play a role in transcriptional regulation during brain development. Although the importance of DNA methylation in brain development is highlighted by the neurodevelopmental deficits associated with mutations in genes including methyl-CpG binding protein 2 (MECP2), our knowledge about the specific methylomic trajectories associated with human neurodevelopment is extremely limited. Here we report an analysis of genome-wide patterns of DNA methylation in 179 human fetal brain samples.
2014-12-19 | GSE58885 | GEO
Project description:Epigenetic processes such as DNA methylation play a key role in regulating tissue-specific and temporally-appropriate patterns of gene expression during development. Our knowledge about temporal changes to the epigenome in the developing human pancreas is limited. In this study we quantified levels of DNA methylation at over 800,000 sites in 112 human fetal pancreatic samples (51 male and 61 female) spanning from 6 to 21 post conception weeks (pcw). We found dramatic changes in DNA methylation across human pancreas development, with >22% of all methylation sites displaying significant changes across developmental age, with the majority of these sites showing stable levels of DNA methylation in the mature pancreas. Sites associated with developmental changes in DNA methylation during fetal pancreas development were significantly underrepresented in promoter regulatory regions but significantly overrepresented in regions flanking CpG islands (shores and shelves) and gene bodies. Highly significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small number of regions showing sex-specific DNA methylation trajectories across pancreas development. Weighted gene correlation network analysis (WGCNA) revealed modules of co-methylated loci associated with developmental age were enriched for genes involved in maturity onset diabetes of the young (MODY) and other metabolic phenotypes. A comparison with developmentally-dynamic patterns of DNA methylation in the developing human brain revealed significant tissue specific differences between the fetal pancreas and the fetal brain. Our data confirms the prenatal period to be a time of dynamic epigenetic changes. To our knowledge, this is the most extensive study of DNA methylation patterns in human fetal pancreatic development.
2024-02-19 | GSE244636 | GEO
Project description:5-hydroxymethylcytosine (5-hmC) is a newly discovered modified form of cytosine that has been suspected to be an important epigenetic modification in neurodevelopment. While DNA methylation dynamics have already been implicated during neurodevelopment, little is known about hydroxymethylation in this process. Here we report DNA hydroxymethylation dynamics during cerebellum development in the human brain. Overall, we find a positive correlation between 5-hmC levels and cerebellum development. Genome-wide profiling reveals that 5-hmC is highly enriched on specific gene regions, including exons and especially the untranslated regions (UTRs), but it is depleted on introns and intergenic regions. Furthermore, we have identified fetus-specific and adult-specific differentially hydroxymethylated regions (DhMRs), most of which overlap with genes and CpG island shores. Surprisingly, during development DhMRs are highly enriched in genes encoding mRNAs that can be regulated by fragile X mental retardation protein (FMRP), some of which are disrupted in autism, as well as in many known autism genes. Our results suggest that 5-hmC-mediated epigenetic regulation may broadly impact the development of the human brain, and its dysregulation could contribute to the molecular pathogenesis of neurodevelopmental disorders. We generated comprehensive genome-wide profiles of 5hmC in human cerebellum.
2012-09-30 | E-GEOD-40539 | biostudies-arrayexpress
Project description:5-hydroxymethylcytosine (5-hmC) is a newly discovered modified form of cytosine that has been suspected to be an important epigenetic modification in neurodevelopment. While DNA methylation dynamics have already been implicated during neurodevelopment, little is known about hydroxymethylation in this process. Here we report DNA hydroxymethylation dynamics during cerebellum development in the human brain. Overall, we find a positive correlation between 5-hmC levels and cerebellum development. Genome-wide profiling reveals that 5-hmC is highly enriched on specific gene regions, including exons and especially the untranslated regions (UTRs), but it is depleted on introns and intergenic regions. Furthermore, we have identified fetus-specific and adult-specific differentially hydroxymethylated regions (DhMRs), most of which overlap with genes and CpG island shores. Surprisingly, during development DhMRs are highly enriched in genes encoding mRNAs that can be regulated by fragile X mental retardation protein (FMRP), some of which are disrupted in autism, as well as in many known autism genes. Our results suggest that 5-hmC-mediated epigenetic regulation may broadly impact the development of the human brain, and its dysregulation could contribute to the molecular pathogenesis of neurodevelopmental disorders.
2012-09-30 | GSE40539 | GEO
Project description:In this study we addressed the question whether changes of DNA hydroxymethylation after X-ray irradiation occur in a random fashion or if they show preferences for specific regions or features. We did not only focus on gene loci and promotor sights but also on gene body hydroxymethylation alterations and associated changes in gene expression. A more profound insight into hydroxymethylation characteristics triggered by radiation could provide clues to mechanisms and consequences of cellular response to irradiation including the immediate consequence of DNA strand breaks associated with active DNA demethylation as well as the long term risk of tumorigenesis or other associated diseases.
2019-01-29 | GSE111437 | GEO
Project description:Background: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development, and there is mounting evidence to support a role for developmentally-regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that disease-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects. 33 post-mortem brain (prefrontal cortex) samples (18 schizophrenia cases and 15 controls) were obtained from Douglas Bell-Canada Brain Bank (DBCBB), Montreal, Canada. Bisulfite converted DNA from these samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.0.
2014-09-13 | E-GEOD-61380 | biostudies-arrayexpress
Project description:X-Ray induced DNA-Hydroxymethylation changes
| PRJNA436999 | ENA
Project description:Background: Despite the significant global loss of DNA hydroxymethylation marks in prostate cancer tissues, the locus-specific role of hydroxymethylation in prostate tumorigenesis is unknown. We characterized hydroxymethylation and methylation marks by performing whole-genome next generation sequencing in representative normal and prostate cancer-derived cell lines in order to determine functional pathways and key genes regulated by these epigenomic modifications in cancer. Results: Our cell line model shows disruption of hydroxymethylation distribution in cancer, with global loss and highly specific gain in promoter and CpG island regions. Significantly, we observed locus-specific retention of hydroxymethylation marks in specific intronic and intergenic regions which may play a novel role in the regulation of gene expression in critical functional pathways, such as BARD1 signaling and steroid hormone receptor signaling in cancer. We confirm a modest correlation of hydroxymethylation with expression in intragenic regions in prostate cancer, while identifying an original role for intergenic hydroxymethylation in differentially expressed regulatory pathways in cancer. We also demonstrate a successful strategy for the identification and validation of key candidate genes from differentially regulated biological pathways in prostate cancer. Conclusion: Our results indicate a distinct function for aberrant hydroxymethylation within each genomic feature in cancer, suggesting a specific and complex role for the deregulation of hydroxymethylation in tumorigenesis, similar to methylation. Subsequently, our characterization of key cellular pathways exhibiting dynamic enrichment patterns for methylation and hydroxymethylation marks may allow us to identify differentially epigenetically modified target genes implicated in prostate cancer tumorigenesis. Methylation profiles of representative normal prostate cell line RWPE-1 and prostate adenocarcinoma cell line 22Rv1 were generated by MBD capture followed by high-throughput sequencing on the HiSeq 2500 (Illumina), in triplicate. Hydroxymethylation profiles of RWPE-1 and 22Rv1 were generated by hMeSeal followed by high-throughput sequencing on the HiSeq 2500 (one replicate each). Additional hydroxymethylation profiling for RWPE-1 was generated by hMeDIP followed by high-throughput sequencing on the HiSeq 2000 (Illumina).
2016-03-15 | E-GEOD-74464 | biostudies-arrayexpress
Project description:Background: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development, and there is mounting evidence to support a role for developmentally-regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that disease-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects. Prefrontal cortex (PFC) and cerebellum samples were obtained from 46 brains archived in the London Brain Bank for Neurodegenerative Disorders (LBBND). Of these 22 were schizophrenia cases, ands of the cases 12 were male.
2014-09-18 | E-GEOD-61431 | biostudies-arrayexpress