Methylation, hydroxymethylation and trancriptome profile of brain regions in yak and cattle
Ontology highlight
ABSTRACT:
ORGANISM(S): yak and cattle
SUBMITTER: Jincheng Zhong
PROVIDER: S-BSST352 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.
| S-EPMC4460470 | biostudies-other
Project description:BackgroundTissues and their component cells have unique DNA methylation profiles comprising DNA methylation patterns of tissue-dependent and differentially methylated regions (T-DMRs). Previous studies reported that DNA methylation plays crucial roles in cell differentiation and development. Here, we investigated the genome-wide DNA methylation profiles of mouse neural progenitors derived from different developmental stages using HpyCH4IV, a methylation-sensitive restriction enzyme that recognizes ACGT residues, which are uniformly distributed across the genome.ResultsUsing a microarray-based genome-wide DNA methylation analysis system focusing on 8.5-kb regions around transcription start sites (TSSs), we analyzed the DNA methylation profiles of mouse neurospheres derived from telencephalons at embryonic days 11.5 (E11.5NSph) and 14.5 (E14.5NSph) and the adult brain (AdBr). We identified T-DMRs with different DNA methylation statuses between E11.5NSph and E14.5NSph at genes involved in neural development and/or associated with neurological disorders in humans, such as Dclk1, Nrcam, Nfia, and Ntng1. These T-DMRs were located not only within 2 kb but also distal (several kbs) from the TSSs, and those hypomethylated in E11.5NSph tended to be in CpG island (CGI-) associated genes. Most T-DMRs that were hypomethylated in neurospheres were also hypomethylated in the AdBr. Interestingly, among the T-DMRs hypomethylated in the progenitors, there were T-DMRs that were hypermethylated in the AdBr. Although certain genes, including Ntng1, had hypermethylated T-DMRs 5' upstream, we identified hypomethylated T-DMRs in the AdBr, 3' downstream from their TSSs. This observation could explain why Ntng1 was highly expressed in the AdBr despite upstream hypermethylation.ConclusionMouse adult brain DNA methylation and gene expression profiles could be attributed to developmental dynamics of T-DMRs in neural-related genes.
| S-EPMC3599493 | biostudies-literature
Project description:Background5-Hydroxymethylcytosine (5hmC) is an oxidation product of 5-methylcytosine (5mC), and adjacent CpG sites in mammalian genome can be co-methylated and co-hydroxymethylated due to the processivity of DNMT and TET enzymes.ResultsWe applied TAB-seq and oxBS-seq to selectively detect 5hmC and 5mC at base resolution in the mouse cortex, olfactory bulb and cerebellum tissues. We found that majority of the called 5hmC CpG sites frequently have 5mC modification simultaneously and are enriched in gene body regions of neuron development-related genes in brain tissues. Strikingly, by a systematic search of regions that show highly coordinated methylation and hydroxymethylation (MHBs and hMHBs), we found that MHBs significantly overlapped with hMHBs in gene body regions. Moreover, using a metric called methylation haplotype load, we defined a subset of 1361 tissue-specific MHBs and 3818 shared MHBs. Shared MHBs with low MHL correspond with developmental enhancers, and tissue-specific MHBs resemble the regulatory elements for tissue identity.ConclusionsOur results provide new insights into the role of coordinately oxidized 5mC to 5hmC as distal regulatory elements may involve in regulating tissue identity.
| S-EPMC6311040 | biostudies-literature
Project description:The role of epigenetics in chronic pain at the supraspinal level is yet to be fully characterized. DNA histone methylation is crucially regulated by de novo methyltransferases (DNMT1-3) and ten-eleven translocation dioxygenases (TET1-3). Evidence has shown that methylation markers are altered in different CNS regions related to nociception, namely the dorsal root ganglia, the spinal cord, and different brain areas. Decreased global methylation was found in the DRG, the prefrontal cortex, and the amygdala, which was associated with decreased DNMT1/3a expression. In contrast, increased methylation levels and mRNA levels of TET1 and TET3 were linked to augmented pain hypersensitivity and allodynia in inflammatory and neuropathic pain models. Since epigenetic mechanisms may be responsible for the regulation and coordination of various transcriptional modifications described in chronic pain states, with this study, we aimed to evaluate the functional role of TET1-3 and DNMT1/3a genes in neuropathic pain in several brain areas. In a spared nerve injury rat model of neuropathic pain, 21 days after surgery, we found increased TET1 expression in the medial prefrontal cortex and decreased expression in the caudate-putamen and the amygdala; TET2 was upregulated in the medial thalamus; TET3 mRNA levels were reduced in the medial prefrontal cortex and the caudate-putamen; and DNMT1 was downregulated in the caudate-putamen and the medial thalamus. No statistically significant changes in expression were observed with DNMT3a. Our results suggest a complex functional role for these genes in different brain areas in the context of neuropathic pain. The notion of DNA methylation and hydroxymethylation being cell-type specific and not tissue specific, as well as the possibility of chronologically differential gene expression after the establishment of neuropathic or inflammatory pain models, ought to be addressed in future studies.
| S-EPMC10138521 | biostudies-literature
Project description:DNA methylation (DNAm) has been considered a promising indicator of biological age in mammals and could be useful to increase the accuracy of phenotypic prediction in livestock. The objectives of this study were to estimate the heritability and age effects of site-specific DNAm (DNAm level) and cumulative DNAm across all sites (DNAm load) in beef cattle. Blood samples were collected from cows ranging from 217 to 3,192 days (0.6 to 8.7 years) of age (n = 136). All animals were genotyped, and DNAm was obtained using the Infinium array HorvathMammalMethylChip40. Genetic parameters for DNAm were obtained from an animal model based on the genomic relationship matrix, including the fixed effects of age and breed composition. Heritability estimates of DNAm levels ranged from 0.18 to 0.72, with a similar average across all regions and chromosomes. Heritability estimate of DNAm load was 0.45. The average age effect on DNAm level varied among genomic regions. The DNAm level across the genome increased with age in the promoter and 5' UTR and decreased in the exonic, intronic, 3' UTR, and intergenic regions. In addition, DNAm level increased with age in regions enriched in CpG and decreased in regions deficient in CpG. Results suggest DNAm profiles are influenced by both genetics and the environmental effect of age in beef cattle.
| S-EPMC9283455 | biostudies-literature
Project description:Zebrafish hematopoietic cells from kidney marrow from zebrafish tet2 mutants were compared to wild-type
2020-09-01 | GSE136761 | GEO
Project description:Autism spectrum disorders (ASD) are increasingly common neurodevelopmental disorders defined clinically by a triad of features including impairment in social interaction, impairment in communication in social situations and restricted and repetitive patterns of behavior and interests, with considerable phenotypic heterogeneity among individuals. Although heritability estimates for ASD are high, conventional genetic-based efforts to identify genes involved in ASD have yielded only few reproducible candidate genes that account for only a small proportion of ASDs. There is mounting evidence to suggest environmental and epigenetic factors play a stronger role in the etiology of ASD than previously thought. To begin to understand the contribution of epigenetics to ASD, we have examined DNA methylation (DNAm) in a pilot study of postmortem brain tissue from 19 autism cases and 21 unrelated controls, among three brain regions including dorsolateral prefrontal cortex, temporal cortex and cerebellum. We measured over 485,000 CpG loci across a diverse set of functionally relevant genomic regions using the Infinium HumanMethylation450 BeadChip and identified four genome-wide significant differentially methylated regions (DMRs) using a bump hunting approach and a permutation-based multiple testing correction method. We replicated 3/4 DMRs identified in our genome-wide screen in a different set of samples and across different brain regions. The DMRs identified in this study represent suggestive evidence for commonly altered methylation sites in ASD and provide several promising new candidate genes.
| S-EPMC4184909 | biostudies-literature
Project description:MotivationThe two major epigenetic modifications of cytosines, 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC), coexist with each other in a range of mammalian cell populations. Increasing evidence points to important roles of 5-hmC in demethylation of 5-mC and epigenomic regulation in development. Recently developed experimental methods allow direct single-base profiling of either 5-hmC or 5-mC. Meaningful analyses seem to require combining these experiments with bisulfite sequencing, but doing so naively produces inconsistent estimates of 5-mC or 5-hmC levels.ResultsWe present a method to jointly model read counts from bisulfite sequencing, oxidative bisulfite sequencing and Tet-Assisted Bisulfite sequencing, providing simultaneous estimates of 5-hmC and 5-mC levels that are consistent across experiment types.Availabilityhttp://smithlab.usc.edu/software/mlml
| S-EPMC3789553 | biostudies-literature
Project description:DNA methylation is a critical epigenetic mark in mammalian cells. Many aspects of DNA methylation maintenance have been characterized; however, the exact kinetics of post-replicative methylation maintenance remain a subject of debate. Here we develop isolation of DNA by 5-ethynyl-deoxyuridine labelling for mass spectrometry (iDEMS), a highly sensitive, quantitative mass spectrometry-based method for measuring DNA modifications on metabolically labelled DNA. iDEMS reveals an unexpectedly hemi-methylated landscape on nascent DNA. Combining iDEMS with metabolic labelling reveals that methylation maintenance is outpaced by cell division in mouse embryonic stem cells. Our approach shows that hydroxymethylation is perpetually asymmetric between sister strands in favour of the parental, template strand. iDEMS can be coupled with immunoprecipitation of chromatin proteins, revealing features of DNA methylation-histone modification crosstalk and suggesting a model for interplay between methylation and nucleosome assembly. iDEMS therefore elucidates long-standing questions about DNA modification propagation and provides an important orthogonal technology to understanding this process in dynamic cellular contexts.
| S-EPMC9859752 | biostudies-literature
Project description:DNA methylation (5mC) plays important roles in mammalian development, oncogenesis, treatment response, and responses to the environment. DNA hydroxymethylation (5hmC) is also an informative epigenetic mark with distinct roles in regulation and cancer. Gold-standard, widely used technologies (bisulfite conversion, followed by deep sequencing) cannot distinguish between 5mC and 5hmC. Therefore, additional experiments are required to differentiate the two marks, and in silico methods are needed to analyze, integrate, and interpret these data. We developed the Methylation INTegration (mint) pipeline to support the comprehensive analysis of bisulfite conversion and immunoprecipitation-based methylation and hydroxymethylation assays, with additional steps toward integration, visualization, and interpretation. The pipeline is available as both a command line and a Galaxy graphical user interface tool. Both implementations require minimal configuration while remaining flexible to experiment specific needs. Cancer Res; 77(21); e27-30. ©2017 AACR.
| S-EPMC5678940 | biostudies-literature