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| Status |
Public on Feb 27, 2014 |
| Title |
Dynamic Reorganization of the Cardiomyocyte Transcriptome in Response to TNFα-induced Proinflammatory Signaling [GRO-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Inflammation is associated with many cardiovascular pathologies, but the underlying mechanisms remain unclear. To explore this in more detail, we characterized the transcriptome of an immortalized adult human ventricular cardiomyocyte cell line (AC16) in response to tumor necrosis factor (TNFa). Using a combination of genomic approaches, including global nuclear run-on sequencing (GRO-seq) and chromatin immunoprecipitation coupled with sequencing (ChIP-seq), we identified ~30,000 transcribed regions in AC16 cells, which includes a set of RNA polymerases I and III (Pol I and Pol III) transcribed regions revealed in the presence of α-amanitin. The set of transcribed regions produces both protein-coding and non-coding RNAs, many of which have not been annotated previously, including enhancer RNAs originating from NF-κB binding sites. In addition, we observed that AC16 cells rapidly and dynamically reorganize their transcriptomes in response to TNFa stimulation in an NF-κB-dependent manner, switching from a basal state to a proinflammatory state affecting a spectrum of cardiac-associated protein-coding and non-coding genes. Moreover, we observed distinct Pol II dynamics for up- and downregulated genes, with a rapid release of Pol II into productive elongation for TNFa-stimulated genes. Our studies shed new light on the regulation of the cardiomyocyte transcriptome in response to a proinflammatory signal and help to clarify the link between inflammation and cardiomyocyte function at the transcriptional level.
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| |
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| Overall design |
Using GRO-seq and ChIP-seq (p65 and RNA Pol II) over a time course of TNFα signaling in AC16 human cardiomyocytes.
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| |
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| Contributor(s) |
Luo X, Chae M, Krishnakumar R, Danko CG, Kraus WL |
| Citation(s) |
24564208 |
| Submission date |
Sep 27, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
W. Lee Kraus |
| E-mail(s) |
lee.kraus@utsouthwestern.edu
|
| Organization name |
UT Southwestern Medical Center
|
| Street address |
5323 Harry Hines Blvd.
|
| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-8511 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE51225 |
Dynamic Reorganization of the Cardiomyocyte Transcriptome in Response to TNFα-induced Proinflammatory Signaling |
|
| Relations |
| BioProject |
PRJNA223649 |
| SRA |
SRP031852 |
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