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TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas

ABSTRACT: TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas

PROVIDER: PRJNA551887 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12748769.fastq.gz	Fastqsanger.gz
	SRR12748770.fastq.gz	Fastqsanger.gz
	SRR12748771.fastq.gz	Fastqsanger.gz
	SRR12748772.fastq.gz	Fastqsanger.gz
	SRR12748773.fastq.gz	Fastqsanger.gz

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TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas [ATAC-seq]

Project description:We investigated the contribution of TOP2B to transcriptional modulation in gliomas given the variable expression of this helicase across tumors, and its emerging role in epigenetic regulation of transcription. We mapped the genomic location of TOP2B, and identified distinct sites of native binding and enzymatic activity across human glioma cell lines and human tumor specimens. TOP2B was active in a subset of promoters and introns, and its inhibition led to downregulation of these genes. We investigated the contribution of TOP2B to transcriptional modulation in gliomas given the variable expression of this helicase across tumors, and its emerging role in epigenetic regulation of transcription. We mapped the genomic location of TOP2B, and identified distinct sites of native binding and enzymatic activity across human glioma cell lines and human tumor specimens. TOP2B was active in a subset of promoters and introns, and its inhibition led to downregulation of these genes.

2020-06-25 | GSE134455 | GEO

TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas [ChIP-seq]

2020-06-25 | GSE133263 | GEO

TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas [RNA-seq]

2020-06-25 | GSE133557 | GEO

TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas [ChIP-seq]

Project description:TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas [ChIP-seq]

| PRJNA550543 | ENA

TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas [ATAC-seq]

Project description:TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas [ATAC-seq]

| PRJNA555430 | ENA

TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas [RNA-seq]

Project description:TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas [RNA-seq]

| PRJNA551885 | ENA

TOP2B Enzymatic Activity on Promoters and Introns Modulates Multiple Oncogenes in Human Gliomas.

Project description:PurposeThe epigenetic mechanisms involved in transcriptional regulation leading to malignant phenotype in gliomas remains poorly understood. Topoisomerase IIB (TOP2B), an enzyme that decoils and releases torsional forces in DNA, is overexpressed in a subset of gliomas. Therefore, we investigated its role in epigenetic regulation in these tumors.Experimental designTo investigate the role of TOP2B in epigenetic regulation in gliomas, we performed paired chromatin immunoprecipitation sequencing for TOP2B and RNA-sequencing analysis of glioma cell lines with and without TOP2B inhibition and in human glioma specimens. These experiments were complemented with assay for transposase-accessible chromatin using sequencing, gene silencing, and mouse xenograft experiments to investigate the function of TOP2B and its role in glioma phenotypes.ResultsWe discovered that TOP2B modulates transcription of multiple oncogenes in human gliomas. TOP2B regulated transcription only at sites where it was enzymatically active, but not at all native binding sites. In particular, TOP2B activity localized in enhancers, promoters, and introns of PDGFRA and MYC, facilitating their expression. TOP2B levels and genomic localization was associated with PDGFRA and MYC expression across glioma specimens, which was not seen in nontumoral human brain tissue. In vivo, TOP2B knockdown of human glioma intracranial implants prolonged survival and downregulated PDGFRA.ConclusionsOur results indicate that TOP2B activity exerts a pleiotropic role in transcriptional regulation of oncogenes in a subset of gliomas promoting a proliferative phenotype.

| S-EPMC8818263 | biostudies-literature

TOP2B binding and enzymatic activity on promoters and introns modulates multiple oncogenes in human gliomas

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-06-25 | GSE133561 | GEO

TOP2B cooperates with ATRX to resolve G-quadruplexes and maintain replication fork stability in glioma

Project description:ATRX is a chromatin remodeling protein that maintains genomic stability by resolving G-quadruplex (G4) DNA structure. However, the details of resolving G4 by ATRX remain unclear. Here, we unveil that TOP2B and ATRX collaborate to maintain genomic stability by regulating G4. ATRX deficiency causes the accumulation of G4 and increases cells’ reliance on TOP2B to resolve G4 structures and maintain replication fork stability. CX-5461, as a TOP2B poison, stabilizes G4 by trapping TOP2B on DNA as well as inhibiting the formation of the ATRX-TOP2B complex and its recruitment to G4 sites. CX-5461 treatment resulted in the entrapment of TOP2B and the subsequent hyperaccumulation of G4 in ATRX-deficient glioma cells, ultimately leading to genomic instability and cell death. Furthermore, we found that YTHDF3 promotes ATRX protein synthesis through m6A modification. Our findings suggest that targeting TOP2B with CX-5461 has therapeutic potential for ATRX-deficient gliomas, offering a promising direction for future treatment strategies.

2025-11-13 | GSE275821 | GEO

Genome wide ChIP-seq analysis of human TOP2B occupancy in MCF7 breast cancer epithelial cells

Project description:TOP2B is involved in transcriptional initiation in response to nuclear hormone ligands and plays a role in transcriptional elongation. Whole genome TOP2B ChIP-seq was carried out on human MCF7 cells in the presence and absence of the nuclear hormone estradiol. Three peak calling methods were used and the peaks identified by at least two methods were analyzed further. Approximately half of the peaks fell either within a gene or within 5Kb of a transcription start site. The coincidence of TOP2B peaks and gene promoters was analyzed; TOP2B peaks were less frequently associated with promoters in estradiol treated than in control cells, suggesting a role of TOP2B in repression of transcription or a transient role in estradiol induced transcriptional changes. Whole genome TOP2B ChIP-seq was carried out on human MCF7 cells in the presence (30 mins exposure) and absence of the nuclear hormone estradiol. "Input" control samples were also sequenced for background detection and comparison.

2015-09-21 | E-GEOD-66753 | biostudies-arrayexpress

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