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Series GSE79951 Query DataSets for GSE79951
Status Public on May 27, 2016
Title Topoisomerase 1 Regulates Gene Expression in Neurons through Cleavage Complex-Dependent and -Independent Mechanisms
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Topoisomerase 1 (TOP1) inhibitors, including camptothecin and topotecan, covalently trap TOP1 on DNA, creating cleavage complexes (cc’s) that must be resolved before gene transcription and DNA replication can proceed. We previously found that topotecan reduces the expression of long (>100 kb) genes and unsilences the paternal allele of Ube3a in neurons. Here, we sought to evaluate overlap between TOP1cc-dependent and -independent gene regulation in neurons. To do this, we utilized Top1 conditional knockout mice, Top1 knockdown, the CRISPR-Cas9 system to delete Top1, TOP1 catalytic inhibitors that do not generate TOP1cc’s, and a TOP1 mutation (T718A) that stabilizes TOP1cc’s. We found that topotecan treatment significantly alters the expression of many more genes, including long neuronal genes, immediate early genes, and paternal Ube3a, when compared to Top1 deletion. Our data show that topotecan has a stronger effect on neuronal transcription than Top1 deletion, and identifies TOP1cc-dependent and -independent contributions to gene expression.
 
Overall design Cortical neurons from WT and Top1 conditional knockout mice, both topotecan-treated and vehicle controls, were processed in triplicate.
Web link http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156439
 
Contributor(s) Simon JM, Mabb AM, Zylka MJ
Citation(s) 27231886
Submission date Apr 05, 2016
Last update date May 15, 2019
Contact name Mark Zylka
Organization name University of North Carolina - Chapel Hill
Street address 5109D Neuroscience Research Building
City Chapel Hill
State/province NC
ZIP/Postal code 27599
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (12)
GSM2109035 WT_Veh_Rep1
GSM2109036 WT_Veh_Rep2
GSM2109037 WT_Veh_Rep3
Relations
BioProject PRJNA317485
SRA SRP072888

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE79951_WT_Top1cKO_Veh_Topot_rawCounts_matrix.txt.gz 332.4 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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