Functional characterization of DNA methylation in the oligodendrocyte lineage
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA275776 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1810030.fastq.gz | Fastqsanger.gz | |||
| SRR1810040_1.fastq.gz | Fastqsanger.gz | |||
| SRR1810040_2.fastq.gz | Fastqsanger.gz | |||
| SRR1810031.fastq.gz | Fastqsanger.gz | |||
| SRR1810041_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Myelination in the CNS is modulated by interplay between transcription factors and recruitment of chromatin modifying enzymes. Using a network built from genome-wide DNA methylation and transcriptomic profiling of sorted oligodendrocyte lineage cells that integrates oligodendrocyte-specific ChIP-Seq data, we defined a crucial role of DNA methylation in coordinating the transition between progenitor cell cycle arrest and oligodendrocyte differentiation. We further identified DNA methyltransferase 1 (DNMT1) as key regulator of oligodendrocyte survival at this transition point, as we detected severe and extensive developmental hypomyelination only in Olig1cre/+;Dnmt1flox/flox but not in Olig1cre/+;Dnmt3aflox/flox mice or in Cnpcre/+;Dnmt1flox/flox. This phenotype was characterized by decreased expression of genes regulating myelination and lipid metabolism â despite the hypomethylation observed at these genetic loci  â and upregulation of cell cycle and DNA-damage pathways. Therefore DNMT1 is a nodal point regulating proliferation, survival, and differentiation in the oligodendrocyte lineage, and is critical for cell number regulation in the developing brain. Genome wide DNA methylation profiles of FAC-sorted P2 Pdgfra::GFP and P18 Plp1-GFP purified cell samples from mouse brains were generated by ERRBS analysis, in duplicate, using Illumina HiSeq 2000.
2016-04-14 | E-GEOD-66028 | biostudies-arrayexpress
Project description:Myelination in the CNS is modulated by interplay between transcription factors and recruitment of chromatin modifying enzymes. Using a network built from genome-wide DNA methylation and transcriptomic profiling of sorted oligodendrocyte lineage cells that integrates oligodendrocyte-specific ChIP-Seq data, we defined a crucial role of DNA methylation in coordinating the transition between progenitor cell cycle arrest and oligodendrocyte differentiation. We further identified DNA methyltransferase 1 (DNMT1) as key regulator of oligodendrocyte survival at this transition point, as we detected severe and extensive developmental hypomyelination only in Olig1cre/+;Dnmt1flox/flox but not in Olig1cre/+;Dnmt3aflox/flox mice or in Cnpcre/+;Dnmt1flox/flox. This phenotype was characterized by decreased expression of genes regulating myelination and lipid metabolism â despite the hypomethylation observed at these genetic loci  â and upregulation of cell cycle and DNA-damage pathways. Therefore DNMT1 is a nodal point regulating proliferation, survival, and differentiation in the oligodendrocyte lineage, and is critical for cell number regulation in the developing brain. mRNA profiles of FAC-sorted P2 Pdgfra::GFP and P18 Plp1-GFP purified cell samples from mouse brains were generated by RNA-sequencing, in triplicate, using Illumina HiSeq 2000.
2016-04-14 | E-GEOD-66029 | biostudies-arrayexpress
Project description:Myelination in the CNS is modulated by interplay between transcription factors and recruitment of chromatin modifying enzymes. Using a network built from genome-wide DNA methylation and transcriptomic profiling of sorted oligodendrocyte lineage cells that integrates oligodendrocyte-specific ChIP-Seq data, we defined a crucial role of DNA methylation in coordinating the transition between progenitor cell cycle arrest and oligodendrocyte differentiation. We further identified DNA methyltransferase 1 (DNMT1) as key regulator of oligodendrocyte survival at this transition point, as we detected severe and extensive developmental hypomyelination only in Olig1cre/+;Dnmt1flox/flox but not in Olig1cre/+;Dnmt3aflox/flox mice or in Cnpcre/+;Dnmt1flox/flox. This phenotype was characterized by decreased expression of genes regulating myelination and lipid metabolism – despite the hypomethylation observed at these genetic loci – and upregulation of cell cycle and DNA-damage pathways. Therefore DNMT1 is a nodal point regulating proliferation, survival, and differentiation in the oligodendrocyte lineage, and is critical for cell number regulation in the developing brain.
2016-04-14 | GSE66029 | GEO
Project description:Myelination in the CNS is modulated by interplay between transcription factors and recruitment of chromatin modifying enzymes. Using a network built from genome-wide DNA methylation and transcriptomic profiling of sorted oligodendrocyte lineage cells that integrates oligodendrocyte-specific ChIP-Seq data, we defined a crucial role of DNA methylation in coordinating the transition between progenitor cell cycle arrest and oligodendrocyte differentiation. We further identified DNA methyltransferase 1 (DNMT1) as key regulator of oligodendrocyte survival at this transition point, as we detected severe and extensive developmental hypomyelination only in Olig1cre/+;Dnmt1flox/flox but not in Olig1cre/+;Dnmt3aflox/flox mice or in Cnpcre/+;Dnmt1flox/flox. This phenotype was characterized by decreased expression of genes regulating myelination and lipid metabolism – despite the hypomethylation observed at these genetic loci – and upregulation of cell cycle and DNA-damage pathways. Therefore DNMT1 is a nodal point regulating proliferation, survival, and differentiation in the oligodendrocyte lineage, and is critical for cell number regulation in the developing brain.
2016-04-14 | GSE66028 | GEO
Project description:Oligodendrocytes derive from progenitors (OPC) through the interplay of epigenetic and transcriptional events. By integrating high-resolution methylomics, RNA-sequencing and multiple transgenic lines, this study defines the role of DNMT1 in developmental myelination. We detected hypermethylation of genes related to cell cycle and neurogenesis during differentiation of OPC, and yet, genetic ablation of Dnmt1 resulted in inefficient OPC expansion and severe hypomyelination associated with ataxia and tremors in mice. This phenotype was not caused by lineage switch or massive apoptosis, but was characterized by a profound defect of differentiation, associated with massive changes in exon-skipping and intron-retention splicing events, and by the activation of an endoplasmic reticulum stress response. Therefore, loss of Dnmt1 in OPC is not sufficient to induce a lineage switch, but acts as an important determinant of the coordination between RNA splicing and protein synthesis, necessary for myelin formation. mRNA profiles of P5 mouse Olig1+/+;Dnmt1flox/flox;Pdgfra-GFP and Olig1cre/+;Dnmt1flox/flox;Pdgfra-GFP sorted OPC were generated by RNA-sequencing, in triplicate, using Illumina HiSeq 2500.
2016-04-14 | E-GEOD-79018 | biostudies-arrayexpress
Project description:Oligodendrocytes derive from progenitors (OPCs) through the interplay of epigenomic and transcriptional events. By integrating high-resolution methylomics, RNA-sequencing, and multiple transgenic lines, this study defines the role of DNMT1 in developmental myelination. We detected hypermethylation of genes related to cell cycle and neurogenesis during differentiation of OPCs, yet genetic ablation of Dnmt1 resulted in inefficient OPC expansion and severe hypomyelination associated with ataxia and tremors in mice. This phenotype was not caused by lineage switch or massive apoptosis but was characterized by a profound defect of differentiation associated with changes in exon-skipping and intron-retention splicing events and by the activation of an endoplasmic reticulum stress response. Therefore, loss of Dnmt1 in OPCs is not sufficient to induce a lineage switch but acts as an important determinant of the coordination between RNA splicing and protein synthesis necessary for myelin formation.
| S-EPMC5063656 | biostudies-literature
Project description:The protein arginine methyl transferase PRMT5 is an enzyme expressed in oligodendrocyte lineage cells and responsible for the symmetric methylation of arginine residues on histone tails. Previous work from our laboratory identified PRMT5 as critical for myelination, due to its transcriptional regulation of survival and early stages of differentiation. However, besides its nuclear localization, PRMT5 is found at high levels in the cytoplasm of oligodendrocyte progenitor cells (OPCs) and yet, its interacting partners and non-histone substrates in this lineage, remain elusive. By using mass spectrometry on protein eluates from extracts generated from OPC and immunoprecipitated with PRMT5 antibodies, we identified 1116 proteins as PRMT5 interacting partners. These proteins are related to molecular functions such as RNA binding, ribosomal structure, nucleotide binding, cadherin and actin binding, GTP and GTPase activity. We then investigated PRMT5 substrates using iTRAQ-based proteomics on protein samples isolated from CRISPR-PRMT5 knockdown immortalized oligodendrocyte progenitors compared to CRISPR-EGFP controls. This analysis identified 169 peptides with statistically different symmetric methylation of arginine residues in the two groups. Those peptides led to 30 unique non-histone substrates of PRMT5. The majority of these proteins were consistent with PRMT5 substrates, previously identified in distinct cancer cell lines (e.g. the transcription factor ZN326), and were functionally related to RNA processing and transport, splicing, regulation of mRNA stability and transcription. In addition, we detected three substrates as unique to the oligodendrocyte lineage and not identified in cancer cells. They included the proline-rich protein PRC2C, involved in methyl-RNA binding, the RNA binding protein KHDR2, regulating splicing events and the heterogeneous nuclear RNA binding protein HNRPD, involved in regulation of RNA stability. Together, these results highlight a cell-specific role of PRMT5 in regulating, not only transcription, but RNA processing and translation in OPCs. (287 WORDS)
2021-11-16 | MSV000088396 | MassIVE
Project description:Oligodendrocytes derive from progenitors (OPC) through the interplay of epigenetic and transcriptional events. By integrating high-resolution methylomics, RNA-sequencing and multiple transgenic lines, this study defines the role of DNMT1 in developmental myelination. We detected hypermethylation of genes related to cell cycle and neurogenesis during differentiation of OPC, and yet, genetic ablation of Dnmt1 resulted in inefficient OPC expansion and severe hypomyelination associated with ataxia and tremors in mice. This phenotype was not caused by lineage switch or massive apoptosis, but was characterized by a profound defect of differentiation, associated with massive changes in exon-skipping and intron-retention splicing events, and by the activation of an endoplasmic reticulum stress response. Therefore, loss of Dnmt1 in OPC is not sufficient to induce a lineage switch, but acts as an important determinant of the coordination between RNA splicing and protein synthesis, necessary for myelin formation.
2016-04-14 | GSE79018 | GEO
Project description:Functional characterization of enhancer evolution in the primate lineage
| PRJNA454716 | ENA
Project description:Oligodendrocytes are responsible for myelin formation and axonal trophic support in the vertebrate CNS. While a number of factors have been discovered that regulate oligodendrocyte lineage progression, the exact molecular mechanisms involved in this process remain unclear. Emerging studies have shown that N6-methyladenosine (m6A), the most common internal RNA modification of mammalian mRNA, plays a critical role in various developmental processes. In this study, we demonstrate that oligodendrocyte lineage progression is accompanied by changes in m6A modification on numerous transcripts. In vivo conditional inactivation in oligodendrocyte lineage cells of an essential m6A writer component, METTL14, results in decreased oligodendrocyte numbers and CNS hypomyelination, although oligodendrocyte precursor cell (OPC) numbers are normal. In vitro Mettl14 ablation disrupts post-mitotic oligodendrocyte maturation. In addition, Mettl14 ablation has distinct effects on OPC and oligodendrocyte transcriptomes. Together, our findings indicate that dynamic RNA methylation plays a critical regulatory role in oligodendrocyte development and CNS myelination.
2020-01-01 | GSE136496 | GEO