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Topoisomerase IIA in Adult NSCs Regulates SVZ Neurogenesis by Transcriptional Activation of Usp37 (RNA-Seq)

ABSTRACT: Topoisomerase IIA in Adult NSCs Regulates SVZ Neurogenesis by Transcriptional Activation of Usp37 (RNA-Seq)

PROVIDER: PRJNA791343 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17297244_1.fastq.gz	Fastqsanger.gz
	SRR17297244_2.fastq.gz	Fastqsanger.gz
	SRR17297245_1.fastq.gz	Fastqsanger.gz
	SRR17297245_2.fastq.gz	Fastqsanger.gz
	SRR17297246_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Topoisomerase IIA in Adult NSCs Regulates SVZ Neurogenesis by Transcriptional Activation of Usp37 (RNA-Seq)

Project description:Topoisomerase IIA (TOP2a) has been traditionally known as an important nuclear enzyme that resolves entanglements and relieves torsional stress of DNA double strands. However, little is known about its function in genomic transcriptional regulation, especially during adult neurogenesis. Here, we show that TOP2a is preferentially expressed in neurogenic niches in the brain of adult mice, such as the subventricular zone (SVZ). Conditional knockout of Top2a in adult neural stem cells (NSCs) in the SVZ significantly inhibits their self-renewal and proliferation and ultimately reduces neurogenesis. To gain insight into the molecular mechanisms by which TOP2a regulates adult NSCs, we perform RNA-sequencing (RNA-Seq) and chromatin immunoprecipitation sequencing (ChIP-Seq) and identify ubiquitin-specific proteases 37 (Usp37) as a direct TOP2a target gene. Importantly, overexpression of Usp37 is sufficient to rescue the impaired self-renewal ability of adult NSCs caused by Top2a knockdown. Taken together, our proof-of-principle study illustrates a TOP2a/Usp37-mediated novel molecular mechanism of adult neurogenesis, which will significantly expand our understanding of the function of topoisomerase in adult brain.

2022-09-20 | GSE192398 | GEO

Topoisomerase IIA in Adult NSCs Regulates SVZ Neurogenesis by Transcriptional Activation of Usp37 (ChIP-Seq)

2022-09-20 | GSE192397 | GEO

Topoisomerase IIA in Adult NSCs Regulates SVZ Neurogenesis by Transcriptional Activation of Usp37 (ChIP-Seq)

Project description:Topoisomerase IIA in Adult NSCs Regulates SVZ Neurogenesis by Transcriptional Activation of Usp37 (ChIP-Seq)

| PRJNA791344 | ENA

Topoisomerase IIA in adult NSCs regulates SVZ neurogenesis by transcriptional activation of Usp37.

Project description:Topoisomerase IIA (TOP2a) has traditionally been known as an important nuclear enzyme that resolves entanglements and relieves torsional stress of DNA double strands. However, its function in genomic transcriptional regulation remains largely unknown, especially during adult neurogenesis. Here, we show that TOP2a is preferentially expressed in neurogenic niches in the brain of adult mice, such as the subventricular zone (SVZ). Conditional knockout of Top2a in adult neural stem cells (NSCs) of the SVZ significantly inhibits their self-renewal and proliferation, and ultimately reduces neurogenesis. To gain insight into the molecular mechanisms by which TOP2a regulates adult NSCs, we perform RNA-sequencing (RNA-Seq) plus chromatin immunoprecipitation sequencing (ChIP-Seq) and identify ubiquitin-specific protease 37 (Usp37) as a direct TOP2a target gene. Importantly, overexpression of Usp37 is sufficient to rescue the impaired self-renewal ability of adult NSCs caused by Top2a knockdown. Taken together, this proof-of-principle study illustrates a TOP2a/Usp37-mediated novel molecular mechanism in adult neurogenesis, which will significantly expand our understanding of the function of topoisomerase in the adult brain.

| S-EPMC9458435 | biostudies-literature

Timecourse analysis of Ezh2-dependent gene expression by SVZ NSCs during differentiation

Project description:Previous work had established that Ezh2-deleted neural stem cells (NSCs) from the postnatal mouse subventricular zone (SVZ) had a deficit in both proliferation and neuronal differentiation both in vivo and in vitro. Ezh2-deleted NSCs in an Ink4a/Arf-deleted background proliferated normally but still displayed a neurogenesis defect, suggesting that Ezh2 is necessary for the proper expression of genes responsible for neuronal differentiation. Our results identify genes that are differentially regulated between control and Ezh2-deleted SVZ NSCs during differentiation. Total RNA obtained from SVZ NSCs 0, 1, 2, 4, and 7 days after switching from proliferation to differentiation media.

2014-05-02 | E-GEOD-56988 | biostudies-arrayexpress

Timecourse analysis of Ezh2-dependent gene expression by SVZ NSCs during differentiation

2014-05-02 | GSE56988 | GEO

Murine postnatal subventricular zone (SVZ) neural stem cells (NSCs): Wild-type (WT) vs. Dnmt3a-null (KO)

2010-06-25 | GSE22473 | GEO

Genome-wide location analysis of Dnmt3a-mediated epigenetic regulation in murine postnatal subventricular zone (SVZ) neural stem cells (NSCs) [NimbleGen]

Project description:DNA methylation at proximal promoters facilitates lineage restriction by silencing cell-type specific genes. However, euchromatic DNA methylation frequently occurs in regions outside promoters. The functions of such non-proximal promoter DNA methylation are unclear. Here we show that the de novo DNA methyltransferase Dnmt3a is expressed in postnatal neural stem cells (NSCs) and is required for neurogenesis. Genome-wide analysis of postnatal NSCs indicates that Dnmt3a occupies and methylates intergenic regions and gene bodies flanking proximal promoters of a large cohort of transcriptionally permissive genes, many of which encode regulators of neurogenesis. Surprisingly, Dnmt3a-dependent non-proximal promoter methylation promotes expression of these neurogenic genes by functionally antagonizing Polycomb repression. Thus, non-promoter DNA methylation by Dnmt3a may be utilized for maintaining active chromatin states of genes critical for development. Chromatin extracted from wild-type (WT) or Dnmt3a-null (KO) SVZ NSCs was immunoprecipitated with indicated antibodies and analyzed by NimbleGen 2.1M mouse whole genome tiling microarrays (a 4-array set covering the entired non-repetitive portion of mouse genome). Whole cell extract (WCE) was used as input controls for IP/WCe experiments. For IP/IP experiments, immunoprecipitated DNA from WT and KO NSCs was directly compared on the same microarrays. For identifying Dnmt3a-dependent DNA methylation at a genome-wide scale, a dye-swap design was employed for comparing DNA methylation levels between WT and KO SVZ NSCs.

2010-06-25 | E-GEOD-22475 | biostudies-arrayexpress

Murine postnatal subventricular zone (SVZ) neural stem cells (NSCs): Wild-type (WT) vs. Dnmt3a-null (KO)

Project description:Transcriptional profiling of mouse postnatal SVZ NSCs comparing WT NSCs with KO NSCs under proliferating/undifferentiated states as well as differentiating conditions. Goal was to determine Dnmt3a-dependent gene expression changes in postnatal SVZ NSCs Two-condition experiment with a dye-swap design, WT NSCs vs. KO NSCs. Biological replicates: 4 replicates under proliferating/undifferentiation conditions, 2 replicates under differentiating conditions.

2010-07-29 | E-GEOD-22473 | biostudies-arrayexpress

Transcriptional impact of conditional loss of Notch2 from adult NSCs

Project description:Adult NSCs maintenance depends on intakt Notch signaling. The role of Notch2 has only been marginally studied in adult neurogenesis. To adress the role of the Notch2 paralogue we conditionally deleted Notch2 from the adult SVZ and analysed the Notch2-deficient cells at distinct time points.

2018-01-23 | GSE99916 | GEO

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