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bioRxiv · 10.1101/2024.10.13.618029

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

Bassing, C.·Oltz, E.·Allyn, B.·Hayer, K.·Oyeniran, C.·Nganga, V.
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Abstract

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 5V{beta} segment, creating long-range contacts with target downstream DJ{beta} segments within the recombination center (RC). CBEs flanking the RC have multiple functions: terminators of LE originating in the V{beta} 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 long-range contacts, indicating that unidirectional loop extrusion from upstream V{beta} segments was sufficient. Thus, V{beta} 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.

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Bassing, C., Oltz, E., Allyn, B., Hayer, K., Oyeniran, C., Nganga, V.. 2024-10-13. Promoter- and Enhancer-Dependent Cohesin Loading Initiates Chromosome Looping to Fold Tcrb Loci for Long-Range Recombination. https://doi.org/10.1101/2024.10.13.618029

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