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Series GSE31655 Query DataSets for GSE31655
Status Public on Jul 30, 2012
Title Dynamic Changes in Ezh2 Gene Occupancy Underlie Its Involvement in Neural Stem Cell Self-Renewal and Differentiation towards Oligodendrocytes
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
The polycomb group protein Ezh2 is an epigenetic repressor of transcription originally found to prevent untimely differentiation of pluripotent embryonic stem cells. We previously demonstrated that Ezh2 is also expressed in multipotent neural stem cells (NSCs). We showed that Ezh2 expression is downregulated during NSC differentiation into astrocytes or neurons. However, high levels of Ezh2 remained present in differentiating oligodendrocytes until myelinating. This study aimed to elucidate the target genes of Ezh2 in NSCs and in premyelinating oligodendrocytes (pOLs).
We performed chromatin immunoprecipitation followed by high-throughput sequencing to detect the target genes of Ezh2 in NSCs and pOLs. We found 1532 target genes of Ezh2 in NSCs. During NSC differentiation, the occupancy of these genes by Ezh2 was alleviated. However, when the NSCs differentiated into oligodendrocytes, 393 of these genes remained targets of Ezh2. Analysis of the target genes indicated that the repressive activity of Ezh2 in NSCs concerns genes involved in stem cell maintenance, in cell cycle control and in preventing neural differentiation. Among the genes in pOLs that were still repressed by Ezh2 were most prominently those associated with neuronal and astrocytic committed cell lineages. Suppression of Ezh2 activity in NSCs caused loss of stem cell characteristics, blocked their proliferation and ultimately induced apoptosis. Suppression of Ezh2 activity in pOLs resulted in derangement of the oligodendrocytic phenotype, due to re-expression of neuronal and astrocytic genes, and ultimately in apoptosis.
Our data indicate that the epigenetic repressor Ezh2 in NSCs is crucial for proliferative activity and maintenance of neural stemness. During differentiation towards oligodendrocytes, Ezh2 repression continues particularly to suppress other neural fate choices. Ezh2 is completely downregulated during differentiation towards neurons and astrocytes allowing transcription of these differentiation programs. The specific fate choice towards astrocytes or neurons is apparently controlled by epigenetic regulators other than Ezh2.
Overall design Examination of Ezh2 target sites in 2 different primary cells types
Contributor(s) Sher F, Boddeke E, Olah M, Copray S
Citation(s) 22808153
Submission date Aug 25, 2011
Last update date May 15, 2019
Contact name Falak Sher
Organization name CHB
Department F.M. Kirby Neurobiology Center
Street address 3 Blackfan Circle, CLs 12220 Center for Life Science Building
City Boston
State/province MA
ZIP/Postal code MA 02115
Country USA
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (3)
GSM786030 Ezh2-ChIP-Seq-NSCs
GSM786031 Ezh2-ChIP-Seq-pOLs
GSM786032 IgG-ChIP-Seq-Control
SRA SRP007943
BioProject PRJNA145403

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Supplementary file Size Download File type/resource
GSE31655_RAW.tar 542.7 Mb (http)(custom) TAR (of BAM, BW, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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