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Ldb1 establishes multi-enhancer networks to regulate gene expression [RNA-seq]

GSE264455 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/11/27 Platform GPL30172
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.
Published in
LDB1 establishes multi-enhancer networks to regulate gene expression
Aboreden NG, Lam JC, Goel VY et al. · Molecular cell 2025 · PMID 39721581 · doi:10.1016/j.molcel.2024.11.037
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Also filed as BioProject PRJNA1102435 and SRA study SRP502937. Searching any of these in the dataset finder brings you back here.

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