Functional characterization of DNA methylation in the oligodendrocyte lineage
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE66047 | GEO | 2016/04/14
SECONDARY ACCESSION(S): PRJNA275776
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-04-14 | E-GEOD-66047 | 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: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: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 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: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 (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: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:This SuperSeries is composed of the SubSeries listed below.
2012-04-10 | GSE34487 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-10-11 | GSE112411 | GEO