Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Characterization of universal features of partially methylated domains across tissues and species

ABSTRACT: Partially methylated domains (PMDs) are a hallmark of epigenomes in reproducible and specific biological contexts, including cancer cells, the placenta, and cultured cell lines. Existing methods for deciding whether PMDs exist in a sample, as well as their identification, are few, often tailored to specific biological questions, and require high coverage samples for accurate identification. In this study, we outline a set of axioms that take a step towards a functional definition for PMDs, describe an improved method for comparable PMD detection across samples with substantially different sequencing depths, and refine the decision criteria for whether a sample contains PMDs using a data-driven approach. Applying our method to 267 methylomes from 7 species, we corroborated recent results regarding the general association between replication timing and PMD state, and report identification of several reproducibly “escapee” genes within late-replicating domains that escape the downregulation and hypomethylation of their immediate genomic neighborhood. We also explored the discordant PMD state of orthologous genes between human and mouse, and observed a directional association of PMD state with gene expression and local gene density. Our improved method makes low-sequencing, population-level studies of PMD variation possible and our results further refine the model of PMD formation as one where sequence context and regional epigenomic features both play a role in gradual genome-wide hypomethylation.

ORGANISM(S): Mus musculus musculus Homo sapiens

PROVIDER: GSE152819 | GEO | 2020/09/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Large-scale methylation domains mark a functional subset of neuronally expressed genes

Project description:DNA methylation is essential for embryonic and neuronal differentiation, but the function of most genomic DNA methylation marks are poorly understood. Generally the human genome is highly methylated (>70%) except for CpG islands and gene promoters. However, it was recently shown that the IMR90 human fetal lung fibroblast cells have large regions of the genome with partially methylated domains (PMDs, <70% average methylation), in contrast to the rest of the genome which is in highly methylated domains (HMDs, >70% average methylation). Using bisulfite conversion followed by high-throughput sequencing (MethylC-seq), we discovered that human SH-SY5Y neuronal cells also contain PMDs. We developed a novel hidden Markov model (HMM) to computationally map the genomic locations of PMDs in both cell types and found that autosomal PMDs can be over 9 Mb in length and cover 41% of the IMR90 genome and 19% of the SH-SY5Y genome. Genomic regions marked by cell line specific PMDs contain genes that are expressed in a tissue-specific manner, with PMDs being a mark of repressed transcription. Genes contained within N-HMDs (neuronal HMDs, defined as a PMD in IMR90 but HMD in SH-SY5Y) were significantly enriched for calcium signaling, synaptic transmission and neuron differentiation functions. Autism candidate genes were enriched within PMDs and the largest PMD observed in SH-SY5Y cells marked a 10 Mb cluster of cadherin genes with strong genetic association to autism. Our results suggest that these large-scale methylation domain maps could be relevant to interpreting and directing future investigations into the elusive etiology of autism. Examined DNA methylation in a human neuronal cell line and cerebral cortex

2011-06-23 | E-GEOD-25930 | biostudies-arrayexpress

Large-scale methylation domains mark a functional subset of neuronally expressed genes

2011-06-23 | GSE25930 | GEO

The effects of postmortem delay on mouse microglia gene expression

Project description:Microglia are specialized macrophages of the central nervous system (CNS) and first to react to pathogens or injury. Transcriptional profiling significantly contributed to our understanding of microglia functions. In the case of human CNS samples, a postmortem delay (PMD) in tissue access and collection is the potential factor that might affect microglia gene expression profiles. However, the direct analysis of effects of PMD on human microglia transcriptome is challenging due to many confounding factors such as sex, aging, nutrition, lifestyle, medication and medical history. To determine the effects of PMD on the microglia transcriptome. Here, we analyzed mouse microglia, where ante-mortem conditions and post-mortem delay can be tightly controlled. PMD had very limited effect on mouse microglia gene expression, only 50 genes (out of 15,554 detected genes) were differentially expressed between different PMDs.

2021-01-01 | GSE162209 | GEO

Examination of gene expression in human placenta using RNA-seq

Project description:As genome-scale DNA methylation sequencing technologies have improved it has become apparent that tissue-specific methylation can occur not only at promoters, enhancers, and CpG islands but also over larger genomic regions. In most human tissues, the vast majority of the genome is highly methylated (>70%). However, genomic sequencing of bisulfite-treated DNA (MethylC-seq) has revealed large partially methylated domains (PMDs) in some human cell lines. However, to date only cultured cells and some cancers have shown evidence for PMDs, suggesting that PMDs may not be observed in normal human tissues. Here we performed MethylC-seq in a set of human tissues and found that full-term human placenta shows clear evidence of PMDs. Examination of gene expression in human placenta using RNA-seq, with one biological replicate (taken from same placenta)

2013-03-28 | E-GEOD-39776 | biostudies-arrayexpress

Examination of four human tissue samples by MethylC-seq

Project description:As genome-scale DNA methylation sequencing technologies have improved it has become apparent that tissue-specific methylation can occur not only at promoters, enhancers, and CpG islands but also over larger genomic regions. In most human tissues, the vast majority of the genome is highly methylated (>70%). However, genomic sequencing of bisulfite-treated DNA (MethylC-seq) has revealed large partially methylated domains (PMDs) in some human cell lines. However, to date only cultured cells and some cancers have shown evidence for PMDs, suggesting that PMDs may not be observed in normal human tissues. Here we performed MethylC-seq in a set of human tissues and found that full-term human placenta shows clear evidence of PMDs. Examination of four human tissue samples by MethylC-seq, with one tissue (placenta) having a technical replicate (taken from same placenta) and two additional biological replicates (from different placentas)

2013-03-28 | E-GEOD-39775 | biostudies-arrayexpress

Examination of four human tissue samples by MethylC-seq

2013-03-28 | GSE39775 | GEO

Examination of gene expression in human placenta using RNA-seq

2013-03-28 | GSE39776 | GEO

Multi-omics analysis of neuroblastoma cells reveals a diversity of malignant transformations

Project description:Neuroblastoma (NB) is a pediatric cancer of the developing sympathetic nervous system that exhibits significant variation in the stage of differentiation and cell composition of tumours. Global loss of DNA methylation and genomic 5-hydroxymethylcytosine (5hmC) is a hallmark of human cancers. Here, we used our recently developed single base resolution approaches, hmTOP-seq and uTOP-seq, for construction of 5hmC maps and identification of large hypomethylated domains (PMDs) in different NB cell subpopulations. The 5hmC profiles revealed distinct signatures characteristic of different cell lineages and stages of malignant transformation of NB cells in a conventional and oxygen depleted environment, which often occurs in tumours. The analysis of the cell type-specific PMD distribution highlighted differences in global genome organization among NB cells that were ascribed to the same lineage identity by transcriptome assays. Collectively, we demonstrated a high informativeness of the integrative epigenomic and transcriptomic research in relation to large scale genome structure in investigating the mechanisms that regulate cell identities and developmental stages of NB cells. Such multi-omics analysis, as compared to mutational studies, open new ways for identification of novel disease-associated features which bring prognostic and therapeutic value in treating this aggressive pediatric disease.

2021-08-19 | GSE130612 | GEO

DNA methylation maintains integrity of higher order genome architecture (Repli-Seq)

Project description:DNA replication timing and 3D chromatin organisation are associated with epigenomic changes across large domains during human differentiation and cancer progression. However, it is unclear if epigenome changes, in particular cancer-associated DNA hypomethylation, is a consequence or cause of changes observed in higher order genome architecture. Here, we compare replication timing profiles and three dimensional (3D) genome organisation, using Hi-C and single cell Repli-Seq in the DNMT1 and DNMT3B DNA methyltransferases double knockout hypomethylated DKO1 colorectal cancer cell line and its parental HCT116 cell line. We find that the hypomethylated cells show a profound loss of replication timing precision, gain of single cell replication timing heterogeneity and loss of chromatin conformation integrity. Discrete regions, that undergo a large change in replication timing in the hypomethylated cells, are associated with a loss of allelic replication timing and shrinking of late replicating Partially Methylated Domain (PMD) boundaries. In contrast, conservation of replication timing after DNA methylation depletion at PMDs is associated with the formation of new H3K9me3/H3K4me3 bivalent domains which may serve to prevent ectopic transcription and maintain cell viability. Together our results show that a loss of global methylation, a common hallmark of cancer, directly impacts on the precision of replication timing and contribute to deregulation of the 3D chromatin architecture.

2021-09-21 | GSE158008 | GEO

DNA methylation maintains integrity of higher order genome architecture (Hi-C)

2021-09-21 | GSE158007 | GEO