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Status |
Public on Jan 22, 2025 |
Title |
Ldb1 establishes multi-enhancer networks to regulate gene expression (TT-seq) |
Organism |
Mus musculus |
Experiment type |
Other
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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 |
Transient transcriptome sequencing (TT-seq) in LDB1-AID cells (untreated and 4 hour auxin-treated conditions).
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Contributor(s) |
Wang S, Aboreden NG, Blobel GA |
Citation(s) |
39721581 |
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Submission date |
Apr 22, 2024 |
Last update date |
Jan 22, 2025 |
Contact name |
Siqing Wang |
E-mail(s) |
wangs16@chop.edu
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Organization name |
Children’s Hospital of Philadelphia
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Department |
Department of Pediatrics, Division of Hematology
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Lab |
Gerd Blobel's Lab
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Street address |
3401 Civic Center Blvd
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City |
Philadelphia |
State/province |
PENNSYLVANIA |
ZIP/Postal code |
19104 |
Country |
USA |
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Platforms (1) |
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Samples (6)
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Relations |
BioProject |
PRJNA1103188 |