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| Status |
Public on Oct 10, 2013 |
| Title |
Gene regulation and priming by Topoisomerase IIα in embryonic stem cells [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Topoisomerases are essential for resolving topological problems in the genome, while their function in gene regulation, especially during cellular differentiation, remains unknown. We reveal that the expression of two Topo II isoforms, Top2a and Top2ß, is characteristic of dividing and postmitotic tissues, respectively. In embryonic stem cells, Top2a preferentially binds to promoters embedded in an active chromatin environment. Inhibition of Top2a activity results in misregulation of target gene expression that accompanies accumulation of double-strand breaks. Common targets of Top2a and Top2ß are housekeeping genes while their unique targets are involved in proliferation/pluripotency and neurogenesis, respectively. Moreover, a subset of Top2a targets exhibit bivalent chromatin state that is resolved upon differentiation concomitant with their activation and occupancy by Top2ß, a feature further observed for long genes. These findings suggest that Top2a not only contributes to stem cell transcriptome regulation but may also prime developmental genes for subsequent activation upon differentiation.
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| Overall design |
mRNA profiles of DMSO and ICRF-193 treated mESCs were generated by deep sequencing in triplicates. ICRF-193 is a well established catalytic inhibitor of Topoisomerase II, hence, we used ICRF-193 to the elucidate role of Top2a catalytic activity on transcription by genome wide transcription profiling.
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| Contributor(s) |
Thakurela S, Garding A, Jung J, Burger L, Tiwari V |
| Citation(s) |
24072229 |
| Submission date |
Apr 15, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Sudhir Thakurela |
| Organization name |
HSCRB
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| Street address |
7 Divinity Avenue
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| City |
Cambridge |
| ZIP/Postal code |
02138 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE46070 |
Gene regulation and priming by Topoisomerase IIα in embryonic stem cells |
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| Relations |
| BioProject |
PRJNA197150 |
| SRA |
SRP021089 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46066_ICRFVsDMSO.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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