Journal article
Promoter- and enhancer-dependent cohesin loading initiates chromosome looping to fold Tcrb loci for long-range recombination
Cell reports (Cambridge), v 44(8), 116133
26 Aug 2025
PMID: 40833849
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cohesin-mediated chromosome looping regulates diverse processes, including antigen receptor (AgR) gene assembly by V(D)J recombination. To understand the mechanisms that coordinate genome topologies, we focused on a genetically tractable AgR locus, Tcrb. Cohesin loading and initiation of loop extrusion (LE) from a nearby CTCF-binding element (CBE) required the promoter of the most 5′Vb segment, creating long-range contacts with downstream DJb segments in the recombination center (RC). CBEs flanking the RC have multiple functions: termination of LE originating in the Vb cluster, initiation of LE in the RC, and insulation of enhancer activity. Deletion of the Tcrb super-enhancer abolished LE from the neighboring RC but spared long-range contacts, indicating that unidirectional LE 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.
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•Promoter-dependent cohesin loading governs loop extrusion and folding of TCRβ loci•Promoter-distal CBEs serve as terminators of loop extrusion to fold TCRβ loci•The TCRβ enhancer is dispensable for promoter-mediated TCRβ folding
Allyn et al. elucidate that TCRβ locus promoters function independently of the TCRβ enhancer to load cohesin, initiate loop extrusion, and fold TCRβ loci for long-range gene assembly.
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Details
- Title
- Promoter- and enhancer-dependent cohesin loading initiates chromosome looping to fold Tcrb loci for long-range recombination
- Creators
- Brittney M. Allyn - Children's Hospital of PhiladelphiaKatharina E. Hayer - Children's Hospital of PhiladelphiaClement Oyeniran - The Ohio State UniversityVincent Nganga - The Ohio State UniversityKyutae Lee - University of PennsylvaniaAhmet Sacan - Drexel UniversityEugene M. Oltz - The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research InstituteCraig H. Bassing (Corresponding Author) - Children's Hospital of Philadelphia
- Publication Details
- Cell reports (Cambridge), v 44(8), 116133
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering and Science
- Web of Science ID
- WOS:001586709900002
- Scopus ID
- 2-s2.0-105013259773
- Other Identifier
- 991022197399004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology