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Rhesus macaque cerebral cortex DNA methylation profiling by MeDIP-Chip

ABSTRACT: The highly improved cognitive function is the most significant change in human evolutionary history. Recently, several large-scale studies reported the evolutionary roles of DNA methylation; however, the role of DNA methylation on brain evolution is largely unknown. To test if DNA methylation has contributed to the evolution of human brain, with the use of MeDIP-Chip and SEQUENOM MassARRAY, we conducted a genome-wide analysis to identify differentially methylated regions (DMRs) in the brain between humans and rhesus macaques. We first identified a total of 150 candidate DMRs by the MeDIP-Chip method, among which 4DMRs were confirmed by the MassARRAY analysis. All 4 DMRs are within or close to the CpG islands, and a MIR3 repeat element was identified in one DMR, but no repeat sequence was observed in the other 3 DMRs. For the 4 DMR genes, their proteins tend to be conserved and two genes have neural related functions. Bisulfite sequencing and phylogenetic comparison among human, chimpanzee, rhesus macaque and rat suggested several regions of lineage specific DNA methylation, including a human specific hypomethylated region in the promoter of K6IRS2 gene. Our study provides a new angle of studying human brain evolution and understanding the evolutionary role of DNA methylation in the central nervous system. The results suggest that the patterns of DNA methylation in the brain are in general similar between humans and non-human primates, and only a few DMRs were identified.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE27460 | GEO | 2012/03/01

SECONDARY ACCESSION(S): PRJNA141753

REPOSITORIES: GEO

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Human cerebral cortex DNA methylation by MeDIP-Chip

Project description:The highly improved cognitive function is the most significant change in human evolutionary history. Recently, several large-scale studies reported the evolutionary roles of DNA methylation; however, the role of DNA methylation on brain evolution is largely unknown. To test if DNA methylation has contributed to the evolution of human brain, with the use of MeDIP-Chip and SEQUENOM MassARRAY, we conducted a genome-wide analysis to identify differentially methylated regions (DMRs) in the brain between humans and rhesus macaques. We first identified a total of 150 candidate DMRs by the MeDIP-Chip method, among which 4DMRs were confirmed by the MassARRAY analysis. All 4 DMRs are within or close to the CpG islands, and a MIR3 repeat element was identified in one DMR, but no repeat sequence was observed in the other 3 DMRs. For the 4 DMR genes, their proteins tend to be conserved and two genes have neural related functions. Bisulfite sequencing and phylogenetic comparison among human, chimpanzee, rhesus macaque and rat suggested several regions of lineage specific DNA methylation, including a human specific hypomethylated region in the promoter of K6IRS2 gene. Our study provides a new angle of studying human brain evolution and understanding the evolutionary role of DNA methylation in the central nervous system. The results suggest that the patterns of DNA methylation in the brain are in general similar between humans and non-human primates, and only a few DMRs were identified.

2012-03-01 | GSE27459 | GEO

Rhesus macaque cerebral cortex DNA methylation profiling by MeDIP-Chip

Project description:Comparing genetic differences between human and nonhuman primates is a fundamental method to dissect the molecular mechanisms underlying the improved human cognitive ability during evolution. Besides DNA sequence divergences, gene regulation differences between human and nonhuman primates have been shown to be more prominent. DNA methylation is an important type of epigenetic modification that plays critical roles in gene regulations. Trans-generational inheritances of DNA methylation in mammals are widely accepted, suggesting the evolutionary role of DNA methylation. To test if DNA methylation has contributed to the evolution of human brain, with the use of MeDIP-Chip and SEQUENOM MassARRAY, we conducted a systematic analysis to identify the differentially methylated DNA regions (DMRs) between human and rhesus macaque in the cerebral cortex. We first identified a total of 150 candidate DMRs by the MeDIP-Chip method, among which 6 DMRs were confirmed by the SEQUENOM MassARRAY method. And 4 of them were further confirmed using independent samples, while the other 2 were failed to test due to technical difficulties. All the 6 DMRs were in CpG islands or close to CpG islands, and a MIR3 repeat element was located in one DMR, but no repeats was found in the other 5 DMRs. For the 6 DMR genes, most have neural related functions, and their proteins tend to be conserved. Additionally, we found the DNA sequence changes at CpG sites contributed to the species-specific DNA methylation. Our study shed light on the researches of trans-generational epigenetic inheritance and the roles of DNA methylation in evolution, especially human evolution. Compare the DNA methylation levels between human and rhesus macaque

2012-03-01 | E-GEOD-27460 | biostudies-arrayexpress

Human cerebral cortex DNA methylation by MeDIP-Chip

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Methylation status in human sperm

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Project description:This study used buccal cells and purified blood monocytes from two different clinical cohorts involving Caucasian or African American female populations with or without arthritis. The differential DNA methylation regions (DMRs) between the control and RA populations were identified using MeDIP-seq. The DMRs (i.e., epimutations) identified in the buccal cells and monocytes were found to be distinct. The DMR associated genes were identified and many have previously been shown to be associated with arthritis. Observations indicate DMRs are cell type specific.

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Evolutionary and functional genomics of DNA methylation in maize domestication and improvement

Project description:DNA methylation is a ubiquitous chromatin feature — in maize, more than 25% of cytosines in the genome are methylated. Recently, major progress has been made in describing the molecular mechanisms driving methylation, yet variation and evolution of the methylation landscape during maize domestication remain largely unknown. Here we leveraged whole-genome sequencing (WGS) and whole-genome bisulfite sequencing (WGBS) on populations of modern maize, landrace, and teosinte (Zea mays ssp. parviglumis) to investigate the adaptive and phenotypic consequences of methylation variations in maize. By using a novel estimation approach, we inferred the methylome site frequency spectrum (mSFS) to estimate forward and backward methylation mutation rates and selection coefficients. We only found weak evidence for direct selection on DNA methylation in any context, but thousands of differentially methylated regions (DMRs) were identified in population-wide that are correlated with recent selection. Further investigation revealed that DMRs are enriched in 5’ untranslated regions, and that maize hypomethylated DMRs likely helped rewire distal gene regulation. For two trait-associated DMRs, vgt1-DMR and tb1DMR, our HiChIP data indicated that the interactive loops between DMRs and respective downstream genes were present in B73, a modern maize line, but absent in teosinte. Functional analyses suggested that these DMRs likely served as cis-acting elements that modulated gene regulation after domestication. Our results enable a better understanding of the evolutionary forces acting on patterns of DNA methylation and suggest a role of methylation variation in adaptive evolution.

2020-09-23 | GSE145586 | GEO

Differential Methylation Of The TRPA1 Promoter In Pain Sensitivity: MeDIP-sequencing

Project description:Chronic pain is a global public health problem, but the underlying molecular mechanisms are not fully understood. Here we examine genome-wide DNA methylation, first in 50 identical twins discordant for heat pain sensitivity and then in 50 further unrelated individuals. Whole blood DNA methylation was characterized at 5.2 million loci by MeDIP-sequencing and assessed longitudinally to identify differentially methylated regions associated with high or low pain-sensitivity (pain-DMRs). Nine meta-analysis pain-DMRs show robust evidence for association (false discovery rate 5%) with the strongest signal in the pain gene TRPA1 (P=1.2M-CM-^W10-13). Several pain-DMRs show longitudinal stability consistent with susceptibility effects, have similar methylation levels in brain, and altered expression in skin. Our approach identifies epigenetic changes in both novel and established candidate genes that provide molecular insights into pain and may generalize to other complex traits. MeDIP-sequencing in 100 individulas using a 2 stage design: paired-end MeDIP-seq in 50 monozygotic twins and single-end MeDIP-seq in 50 unrelated individuals.

2013-12-04 | E-GEOD-52965 | biostudies-arrayexpress

Integrative epigenomic analysis of differential DNA methylation in bladder cancer

Project description:Background Urothelial carcinoma of the bladder (UC) is a common malignancy. Although extensive transcriptome analysis has provided insights into the gene expression patterns of this tumor type, the mechanistic underpinnings of differential methylation remain poorly understood. Multi-level genomic data may be used to profile the regulatory potential and landscape of differential methylation in cancer and gain understanding of the processes underlying epigenetic and phenotypic characteristics of tumors. Methods We perform genome-wide DNA methylation profiling of 98 gene-expression subtyped tumors to identify between-tumor differentially methylated regions (DMRs). We integrate multi-level publically available genomic data generated by the ENCODE consortium to characterize the regulatory potential of UC DMRs. Results We identify 5,453 between-tumor DMRs and derive four DNA methylation subgroups of UC with distinct associations to clinicopathological features and gene expression subtypes. We characterize three distinct patterns of differential methylation and use ENCODE data to show that tumor subgroup-defining DMRs display differential chromatin state, and regulatory factor binding preferences. Finally, we characterize an epigenetic switch involving the HOXA-genes with associations to tumor differentiation states and patient prognosis. Conclusions Genome-wide DMR methylation patterns are reflected in the gene expression subtypes of UC. UC DMRs display three distinct methylation patterns, each associated with intrinsic features of the genome and differential regulatory factor binding preferences. Epigenetic inactivation of HOX-genes correlates with tumor differentiation states and may present an actionable epigenetic alteration in UC. MeDIP hybridizations on 98 human urothelial carcinoma samples and 4 normal urothelium samples on Nimblegen 3x720K RefSeq Promoter and CGI aCGH arrays.

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