Base-resolution analyses of parent-of-origin and sequence dependent allele specific DNA methylation in the mouse genome (MRE-seq)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE33579 | GEO | 2012/02/15
SECONDARY ACCESSION(S): PRJNA154345
REPOSITORIES: GEO
Similar Datasets
Project description:Allele specific DNA methylation (ASM) is crucial for genomic imprinting and mammalian development. Here we present a base-resolution, genome-wide allelic DNA methylation map for both CG and non-CG sites in the mouse brain. We found parent-of-origin dependent (imprinted) ASM at 1,952 CGs which form 55 discrete clusters. This uncovers 31 reported differentially methylated regions (DMRs), including virtually all known germline DMRs, and 24 novel candidate DMRs with some occurring at microRNA genes. In the same adult tissue we also report a surprising presence of non-CG methylation with some showing evidence of imprinting. Finally, we identified sequence dependent ASM at 131,765 CGs. Interestingly, methylation at these sites exhibits a strong dependence on the immediate adjacent bases, allowing us to define a conserved sequence preference for the mammalian DNA methylation machinery. Our genome-wide ASM map should help with understanding the epigenetic differences between two parental genomes in mammals. The crosses of the two mouse strains 129x1/SvJ (129) and Cast/EiJ (Cast) were performed at Jackson Laboratories (http://jaxmice.jax.org/) and the male mice F1 offspring and males of each of the two parental strains were shipped to investigator laboratories at 8 to 9 weeks of age. A total of 500ng genomic DNA isolated from IMR90, MEF, and the frontal cortex of F1i and F1r was digested in parallel by the DNA methylation dependent restriction enzyme FspEI. FspEI recognizes the CmC site (the second cytosine is methylated and can be in the context of CG, CHG or CHH) and creates a 5 protruding end 17 bases downstream of the methylcytosine. A similar experiment was performed by incubating the F1i genomic DNA with a DNA methylation independent restriction enzyme BstNI. The digested DNA was gel purified, size selected for fragments within 100-600bp. The resulting DNA was then prepared as genomic DNA libraries for high-throughput sequencing (Illumina).
2012-02-15 | E-GEOD-33579 | biostudies-arrayexpress
Project description:Allele specific DNA methylation (ASM) is crucial for genomic imprinting and mammalian development. Here we present a base-resolution, genome-wide allelic DNA methylation map for both CG and non-CG sites in the mouse brain. We found parent-of-origin dependent (imprinted) ASM at 1,952 CGs which form 55 discrete clusters. This uncovers 31 reported differentially methylated regions (DMRs), including virtually all known germline DMRs, and 24 novel candidate DMRs with some occurring at microRNA genes. In the same adult tissue we also report a surprising presence of non-CG methylation with some showing evidence of imprinting. Finally, we identified sequence dependent ASM at 131,765 CGs. Interestingly, methylation at these sites exhibits a strong dependence on the immediate adjacent bases, allowing us to define a conserved sequence preference for the mammalian DNA methylation machinery. Our genome-wide ASM map should help with understanding the epigenetic differences between two parental genomes in mammals.
2012-02-15 | GSE33468 | GEO
Project description:Allele specific DNA methylation (ASM) is crucial for genomic imprinting and mammalian development. Here we present a base-resolution, genome-wide allelic DNA methylation map for both CG and non-CG sites in the mouse brain. We found parent-of-origin dependent (imprinted) ASM at 1,952 CGs which form 55 discrete clusters. This uncovers 31 reported differentially methylated regions (DMRs), including virtually all known germline DMRs, and 24 novel candidate DMRs with some occurring at microRNA genes. In the same adult tissue we also report a surprising presence of non-CG methylation with some showing evidence of imprinting. Finally, we identified sequence dependent ASM at 131,765 CGs. Interestingly, methylation at these sites exhibits a strong dependence on the immediate adjacent bases, allowing us to define a conserved sequence preference for the mammalian DNA methylation machinery. Our genome-wide ASM map should help with understanding the epigenetic differences between two parental genomes in mammals.
2012-02-15 | GSE30199 | GEO
Project description:Allele specific DNA methylation (ASM) is crucial for genomic imprinting and mammalian development. Here we present a base-resolution, genome-wide allelic DNA methylation map for both CG and non-CG sites in the mouse brain. We found parent-of-origin dependent (imprinted) ASM at 1,952 CGs which form 55 discrete clusters. This uncovers 31 reported differentially methylated regions (DMRs), including virtually all known germline DMRs, and 24 novel candidate DMRs with some occurring at microRNA genes. In the same adult tissue we also report a surprising presence of non-CG methylation with some showing evidence of imprinting. Finally, we identified sequence dependent ASM at 131,765 CGs. Interestingly, methylation at these sites exhibits a strong dependence on the immediate adjacent bases, allowing us to define a conserved sequence preference for the mammalian DNA methylation machinery. Our genome-wide ASM map should help with understanding the epigenetic differences between two parental genomes in mammals. The crosses of the two mouse strains 129x1/SvJ (129) and Cast/EiJ (Cast) were performed at Jackson Laboratories (http://jaxmice.jax.org/) and the male mice F1 offspring and males of each of the two parental strains were shipped to investigator laboratories at 8 to 9 weeks of age. The frontal cortex from the F1 crosses of the two mouse lines was dissected and the RNA was isolated followed by two DNAseI treatments to remove DNA contaminant. The presence of DNA in the RNA was tested using quantitative PCR and probes designed to span exons. The quality of the RNA was determined by the Agilent 2100 Bioanalyzer prior to the construction of the libraries. RNA was treated with RiboMinus (Invitrogen, Carlsbad CA) to remove the ribosomal RNA. The methods for the preparation of the libraries are outlined in the Whole Transcriptome library preparation for SOLiD sequencing protocol (https://www3.appliedbiosystems.com/cms/groups/mcb_support/documents/generaldocuments/cms_065852.pdf). Briefly, RNA depleted of ribosomal RNA was fragmented using RNAseIII. Purified RNA was hybridized and ligated to primers then converted to cDNA using reverse transcriptase. The cDNA was size selected to contain 50 to 150 bp inserts then purified and amplified prior to sequencing. Libraries were constructed with RNA from three independent mice (3 biological replicates) for each of the experimental crosses. Sequencing was performed at EdgeBio (http://www.edgebio.com/) and the data from the 3 mice for each experimental cross line were combined given the high correlation between each of the libraries (R >0.98).
2012-02-15 | E-GEOD-33468 | biostudies-arrayexpress
Project description:As a key epigenetic modification, DNA methylation is essential for normal development by regulating processes like gene expression, genomic imprinting, and suppression of repetitive elements. However, DNA methylation in the cattle genome is not well understood. Here we presented the first single-base-resolution maps of DNA methylation in 10 diversely somatic tissues harvested from the sequenced Hereford cow L1 Dominette 01449 and her relatives using reduced representation bisulphite sequencing (RRBS). In total, we observed 1,868,049 high accuracy cytosines that located in the CG enriched regions. Similar to the methylation patterning in other species, the CG context was predominant methylated. Widespread differences were identified between the methylation patterns of CG and non-CG contexts. They were distributed differentially among the genomic features, including the genic regions, CpG islands, and repetitive sequences. Autocorrelation analysis among adjacent residues illustrated that methylation level of CGs were highly correlated in a region. In contrast, weak or no correlation was found among non-CGs or between CGs and non-CGs. The distinct distribution and low correlation of CG and non-CG methylation suggested that non-CG methylation may be independent from CG methylation and may be mediated by different mechanisms. We also detected 798 tissue-specific differentially methylated cytosines (tDMC) and 131 tissue-specific differentially methylated CpG islands. Combined analysis with the RNA-seq data, we discovered several non-CGs in tDMCs also highly correlated with gene expression, which implied the potential function of non-CG methylation in somatic cells in addition to pluripotent cells. In summary, we showed that non-CGs exist in bovine tissues and some of them were correlated with tissue-specific functions. This study provided essential information for the cytosine methylation patterning in bovine somatic tissues.
2017-02-14 | GSE76346 | GEO
Project description:As a key epigenetic modification, DNA methylation is essential for normal development by regulating processes like gene expression, genomic imprinting, and suppression of repetitive elements. However, DNA methylation in the cattle genome is not well understood. Here we presented the first single-base-resolution maps of DNA methylation in 10 diversely somatic tissues harvested from the sequenced Hereford cow L1 Dominette 01449 and her relatives using reduced representation bisulphite sequencing (RRBS). In total, we observed 1,868,049 high accuracy cytosines that located in the CG enriched regions. Similar to the methylation patterning in other species, the CG context was predominant methylated. Widespread differences were identified between the methylation patterns of CG and non-CG contexts. They were distributed differentially among the genomic features, including the genic regions, CpG islands, and repetitive sequences. Autocorrelation analysis among adjacent residues illustrated that methylation level of CGs were highly correlated in a region. In contrast, weak or no correlation was found among non-CGs or between CGs and non-CGs. The distinct distribution and low correlation of CG and non-CG methylation suggested that non-CG methylation may be independent from CG methylation and may be mediated by different mechanisms. We also detected 798 tissue-specific differentially methylated cytosines (tDMC) and 131 tissue-specific differentially methylated CpG islands. Combined analysis with the RNA-seq data, we discovered several non-CGs in tDMCs also highly correlated with gene expression, which implied the potential function of non-CG methylation in somatic cells in addition to pluripotent cells. In summary, we showed that non-CGs exist in bovine tissues and some of them were correlated with tissue-specific functions. This study provided essential information for the cytosine methylation patterning in bovine somatic tissues.
2017-02-14 | GSE86323 | GEO
Project description:Haplotype-dependent allele-specific methylation (hap-ASM) can impact disease susceptibility, but maps of this phenomenon using stringent criteria in disease-relevant tissues remain sparse. Here we apply array-based and Methyl-seq approaches to multiple human tissues and cell types, including brain, purified neurons and glia, T lymphocytes, and placenta, and identify 795 hap-ASM differentially methylated regions (DMRs) and 3,082 strong methylation quantitative trait loci (mQTLs), most not previously reported. More than half of these DMRs have cell type-restricted ASM, and among them are 188 hap-ASM DMRs and 933 mQTLs located near GWAS signals for immune and neurological disorders. Targeted bis-seq confirmed hap-ASM in 12/13 loci tested, including CCDC155, CD69, FRMD1, IRF1, KBTBD11, and S100A*-ILF2, associated with immune phenotypes, MYT1L, PTPRN2,CMTM8 and CELF2, associated with neurological disorders, NGFR and HLA-DRB6, associated with both immunological and brain disorders, and ZFP57, a trans-acting regulator of genomic imprinting. Polymorphic CTCF and transcription factor (TF) binding sites are over-represented among hap-ASM DMRs and mQTLs, and analysis of the human data, supplemented by cross-species comparisons to Macaca mulattamacaques, indicates that CTCF and TF binding likelihood predicts the strength and direction of the allelic methylation asymmetry. These results show that hap-ASM is highly tissue-specific; an important trans-acting regulator of genomic imprinting is regulated by this phenomenon; variation in CTCF and TF binding sites is an underlying mechanism in primary tissues, and maps of hap-ASM and mQTLs reveal regulatory sequences underlying supera- and sub-threshold GWAS peaks in immunological and neurological disorders.
2016-03-21 | GSE79254 | GEO
Project description:Haplotype-dependent allele-specific methylation (hap-ASM) can impact disease susceptibility, but maps of this phenomenon using stringent criteria in disease-relevant tissues remain sparse. Here we apply array-based and Methyl-seq approaches to multiple human tissues and cell types, including brain, purified neurons and glia, T lymphocytes, and placenta, and identify 795 hap-ASM differentially methylated regions (DMRs) and 3,082 strong methylation quantitative trait loci (mQTLs), most not previously reported. More than half of these DMRs have cell type-restricted ASM, and among them are 188 hap-ASM DMRs and 933 mQTLs located near GWAS signals for immune and neurological disorders. Targeted bis-seq confirmed hap-ASM in 12/13 loci tested, including CCDC155, CD69, FRMD1, IRF1, KBTBD11, and S100A*-ILF2, associated with immune phenotypes, MYT1L, PTPRN2,CMTM8 and CELF2, associated with neurological disorders, NGFR and HLA-DRB6, associated with both immunological and brain disorders, and ZFP57, a trans-acting regulator of genomic imprinting. Polymorphic CTCF and transcription factor (TF) binding sites are over-represented among hap-ASM DMRs and mQTLs, and analysis of the human data, supplemented by cross-species comparisons to Macaca mulattamacaques, indicates that CTCF and TF binding likelihood predicts the strength and direction of the allelic methylation asymmetry. These results show that hap-ASM is highly tissue-specific; an important trans-acting regulator of genomic imprinting is regulated by this phenomenon; variation in CTCF and TF binding sites is an underlying mechanism in primary tissues, and maps of hap-ASM and mQTLs reveal regulatory sequences underlying supera- and sub-threshold GWAS peaks in immunological and neurological disorders.
2016-03-21 | GSE79148 | GEO
Project description:Haplotype-dependent allele-specific methylation (hap-ASM) can impact disease susceptibility, but maps of this phenomenon using stringent criteria in disease-relevant tissues remain sparse. Here we apply array-based and Methyl-seq approaches to multiple human tissues and cell types, including brain, purified neurons and glia, T lymphocytes, and placenta, and identify 795 hap-ASM differentially methylated regions (DMRs) and 3,082 strong methylation quantitative trait loci (mQTLs), most not previously reported. More than half of these DMRs have cell type-restricted ASM, and among them are 188 hap-ASM DMRs and 933 mQTLs located near GWAS signals for immune and neurological disorders. Targeted bis-seq confirmed hap-ASM in 12/13 loci tested, including CCDC155, CD69, FRMD1, IRF1, KBTBD11, and S100A*-ILF2, associated with immune phenotypes, MYT1L, PTPRN2,CMTM8 and CELF2, associated with neurological disorders, NGFR and HLA-DRB6, associated with both immunological and brain disorders, and ZFP57, a trans-acting regulator of genomic imprinting. Polymorphic CTCF and transcription factor (TF) binding sites are over-represented among hap-ASM DMRs and mQTLs, and analysis of the human data, supplemented by cross-species comparisons to Macaca mulattamacaques, indicates that CTCF and TF binding likelihood predicts the strength and direction of the allelic methylation asymmetry. These results show that hap-ASM is highly tissue-specific; an important trans-acting regulator of genomic imprinting is regulated by this phenomenon; variation in CTCF and TF binding sites is an underlying mechanism in primary tissues, and maps of hap-ASM and mQTLs reveal regulatory sequences underlying supera- and sub-threshold GWAS peaks in immunological and neurological disorders.
2016-03-21 | GSE79144 | GEO
Project description:Genomic imprinting is a mechanism in which the expression of genes varies depending on their parent-of-origin. Imprinting occurs through differential DNA methylation and histone modifications on the two parental alleles, with most imprinted genes marked by CpG-rich differentially methylated regions (DMRs). DNA methylation profiling in cases of uniparental disomy (UPD) provides a unique system permitting the study of DNA derived from a single parent (PMID: 20631049). Approximately 70 human imprinted genes have been described, and imprinted loci have been associated with diseases such as diabetes and cancer. We profiled parent of origin DNA methylation marks to find novel imprinted loci. Methods: We have an unprecedented collection of whole blood DNA from XX patients with UPD covering 18 different chromosomes, allowing for the efficient detection of DMRs associated with imprinted genes for 84% of the human genome. Our study is complimented with Ovarian Teratoma DNA (maternal DNA) and Complete hydatidiform Mole (paternal DNA). DNA methylation was profiled using Illumina Infinium 450K Methylation BeadArrays. Imprinted DMRs were defined by sites at which the maternal and paternal methylation levels diverged significantly from the biparental average. We confirmed novel DMRs by bisulfite sequencing of informative trios and SequenomEpiTYPER assays. Allelic specific gene expression studies were also performed by RNA sequencing in independent biparental controls. Findings: Our results provide for the first comprehensive map of the human imprintome, doubling the number of known imprinted regions. We identified a total of 71 DMRs, 41 of which were novel. 27 novel DMRs were maternally methylated and 14 were paternally methylated. We identified DMRs on chromosomes 5, 21 and 22 previously considered devoid of imprinting, highlighting potential parent-of-origin effects in chromosomal aneuploidies such as Down syndrome. We also found DMRs in genes associated with Schizophrenia and epilepsy. Interpretation: Our data provide the first comprehensive genome-wide map of imprinted sites in the human genome, and provide novel insights into potential parent-of-origin effects in human disorders. 66 UPD samples analyzed in total, From each individual, whole bllod DNA was extracted and global DNA methylation levels were assessed using Illumina Infinium HumanMethylation450 BeadChip.
2016-06-01 | E-GEOD-64244 | biostudies-arrayexpress