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| Status |
Public on Oct 01, 2017 |
| Title |
CTCF-mediated enhancer-promoter interaction is a critical regulator of cell-to-cell variation of gene expression |
| Organism |
Mus musculus |
| Experiment type |
Other
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
Recent studies indicate that even a homogeneous population of cells display heterogeneity in gene expression and response to environmental stimuli. Although promoter structure critically influences the cell-to-cell variation of gene expression in bacteria and lower eukaryotes, it remains unclear what controls the gene expression noise in mammals. Here we report that CTCF decreases cell-to-cell variation of expression by stabilizing enhancer-promoter interaction. We show that CTCF binding sites are interwoven with enhancers within topologically-associated domains (TADs) and a positive correlation is found between CTCF binding and the activity of the associated enhancers. Deletion of CTCF sites using CRISPR/Cas9 compromises enhancer-promoter interactions. Using single-cell flow cytometry and single-molecule RNA-FISH assays, we demonstrate that knocking down of CTCF or deletion of a CTCF binding site results in increased cell-to-cell variation of gene expression, indicating that long-range promoter-enhancer interaction mediated by CTCF plays an important role in controlling the cell-to-cell variation of gene expression in mammalian cells.
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| Overall design |
¬ 3e Hi-C is a robust technique to measure genome-wide chromatin interactions
¬ CTCF binding is positively correlated with the activity of enhancers and their interaction with target promoters
¬ Knocking down CTCF expression or deletion of CTCF binding sites results in decreased enhancer-promoter interaction and increased cell-to-cell variation of gene expression
¬ CTCF stabilizes enhancer-promoter interaction and controls gene expression noise.
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| |
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| Contributor(s) |
Ren G, Jin W, Cui K, Zhao K |
| Citation(s) |
28938092 |
| |
| Submission date |
Feb 26, 2015 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Keji Zhao |
| Organization name |
NHLBI,NIH
|
| Department |
Systems Biology Center
|
| Lab |
Laboratory of Epigenome Biology
|
| Street address |
9000 Rockville Pike
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA276568 |
| SRA |
SRP055555 |
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