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| Status |
Public on Aug 30, 2017 |
| Title |
Loss of CTCF reveals basic properties of post-mitotic epigenomes and induces heart failure [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Understanding the principles of endogenous chromatin structure has key implications for epigenetic therapy. To determine the mechanisms of genome structure-function in post-mitotic cells, genome-wide chromatin conformation capture was performed in cardiac myocytes, a non-dividing, differentiated cell responsible for cardiac contraction. Cardiac-specific CTCF knockout mice demonstrated that loss of CTCF had minimal effect on topologically associating domains; however, it selectively altered boundary strength and A/B compartmentalization, with gene expression changes mimicking those in heart failure. Loss of CTCF (or subjecting wild-type mice to clinically relevant pressure overload stress) remodeled long-range chromatin looping to alter 3D proximity of enhancers and disease causing genes. Depletion of CTCF was sufficient to induce heart failure in mice and human heart failure patients receiving mechanical unloading to attenuate disease progression show increased CTCF expression. These findings establish CTCF in the maintenance of chromatin looping and identify global chromatin remodeling as a causative factor in heart failure.
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| Overall design |
Control, CTCF knockout, and pressure overload RNA-seq experiments in isolated cardiac myocytes
TAC (transverse aortic constriction) samples represent mouse with diseased hearts.
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| Contributor(s) |
Vondriska TM, Rosa-Garrido M, Chapski DJ |
| Citation(s) |
28802249 |
| |
| Submission date |
Mar 16, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Tom Vondriska |
| E-mail(s) |
vondriska.web@gmail.com
|
| Organization name |
UCLA
|
| Street address |
650 Charles E Young Dr, BH553
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE96693 |
Loss of CTCF reveals basic properties of post-mitotic epigenomes and induces heart failure |
|
| Relations |
| BioProject |
PRJNA379887 |
| SRA |
SRP102228 |
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