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Promoter- and Enhancer-Dependent Cohesin Loading Initiates Chromosome Looping to Fold Tcrb Loci for Long-Range Recombination [ChIP-Seq]

GSE296303 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2025/06/23 Platform GPL24247
Summary
Cohesin-mediated chromosome looping regulates diverse processes, including antigen receptor (AgR) gene assembly by V(D)J recombination. To understand mechanisms that coordinate genome topologies, we focused on a genetically tractable AgR locus, Tcrb. Cohesin loading and initiating loop extrusion (LE) from a nearby CTCF-binding element (CBE) required the promoter of the most 5’Vb segment, creating long-range contacts with target downstream DJb segments within the recombination center (RC). CBEs flanking the RC have multiple functions: terminators of LE originating in the Vb cluster, initiators of LE in the RC, and insulation of enhancer activity. Deletion of the Tcrb super-enhancer abolished loop extrusion from the neighboring RC but spared longrange contacts, indicating that unidirectional loop extrusion from upstream Vb segments was sufficient. Thus, Vb promoter- or enhancer-dependent cohesin loading initiates LE in opposite directions across the locus to assemble a broad Tcrb repertoire, a finding that has broad implications for genomic architecture and function.
Published in
Promoter- and enhancer-dependent cohesin loading initiates chromosome looping to fold Tcrb loci for long-range recombination
Allyn BM, Hayer KE, Oyeniran C et al. · Cell reports 2025 · PMID 40833849 · doi:10.1016/j.celrep.2025.116133
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Also filed as BioProject PRJNA1258896 and SRA study SRP583222. Searching any of these in the dataset finder brings you back here.

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