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| Status |
Public on Nov 27, 2024 |
| Title |
Ldb1 establishes multi-enhancer networks to regulate gene expression [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
How enhancers specifically connect to gene promoters is still unclear. Besides the CTCF/cohesin machinery, only a small set of nuclear factors have been studied for a direct role in physically connecting regulatory elements. Here, we show via acute degradation experiments that LDB1 directly and broadly promotes enhancer-promoter loops. Utilizing multiple degron systems, we demonstrate that most endogenous LDB1-mediated contacts can form in the absence of CTCF, cohesin and YY1. Furthermore, an engineered/forced, LDB1-driven chromatin loop can form in the absence of cohesin. Yet, in a fraction of cases cohesin driven extrusion may promote LDB1 anchored loops. Leveraging the dynamic reorganization of nuclear architecture during the transition from mitosis to G1 phase, we establish a relationship between LDB1-dependent interactions in the context of TAD organization and gene activation. Tri-C and Region Capture Micro-C reveal that LDB1 organizes multi-enhancer networks to activate transcription. This establishes LDB1 as direct driver of connectivity between regulatory elements.
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| Overall design |
RNA-seq in parental G1E-ER4 cells and two LDB1-AID-mCherry clones under untreated conditions. To measure concordance amongst transcriptomes between clonal lines expressing the LDB1-AID-mCherry fusion protein compared to parental G1E-ER4 cells.
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| Contributor(s) |
Aboreden NG, Blobel GA |
| Citation missing |
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| Submission date |
Apr 19, 2024 |
| Last update date |
Nov 27, 2024 |
| Contact name |
Nicholas Aboreden |
| E-mail(s) |
[email protected]
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| Organization name |
University of Pennsylvania
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| Lab |
Blobel Lab
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| Street address |
3615 Civic Center Blvd
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1102435 |
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