{"doi":"10.1101/2020.06.30.181222","title":"Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination","abstract":"Abstract Immunoglobulin heavy chain locus ( Igh ) V H , D, and J H gene segments are developmentally assembled into V(D)J exons. RAG endonuclease initiates V(D)J recombination by binding a J H -recombination signal sequence (RSS) within a chromatin-based recombination center (RC) and then, in an orientation-dependent process, scans upstream D-containing chromatin presented by cohesin-mediated loop extrusion for convergent D-RSSs to initiate DJ H -RC formation 1,2 . In primary pro-B cells, 100s of upstream V H -associated RSSs, embedded in convergent orientation to the DJ H -RC-RSS, gain proximity to the DJ H -RC for V H -to-DJ H joining via a mechanistically-undefined V H -locus contraction process 3-7 . Here, we report that a 2.4 mega-base V H locus inversion in primary pro-B cells nearly abrogates rearrangements of normally convergent V H -RSSs and cryptic RSSs, even though locus contraction per se is maintained. Moreover, this inversion activated rearrangement of both cryptic V H -locus RSSs normally in the opposite orientation and, unexpectedly, of normally-oriented cryptic RSSs within multiple, sequential upstream convergent-CBE domains. Primary pro-B cells had significantly reduced transcription of Wapl 8 , a cohesin-unloading factor, versus levels in v-Abl pro-B lines that lack marked locus contraction or distal V H rearrangements 2,9-11 . Correspondingly, Wapl depletion in v-Abl lines activated V H -locus contraction and orientation-specific RAG-scanning across the V H -locus. Our findings indicate that locus contraction and physiological V H -to-DJ H joining both are regulated via circumvention of CBE scanning impediments.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122187,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":562978,"name":"Hongli Hu","orcid":"0000-0003-1932-5027","position":1,"is_corresponding":false},{"id":555064,"name":"Jiangman Lou","orcid":null,"position":2,"is_corresponding":false},{"id":33696,"name":"Adam Yongxin Ye","orcid":"0000-0002-1542-0740","position":3,"is_corresponding":false},{"id":562979,"name":"Aimee Williams","orcid":"0000-0001-9402-4326","position":4,"is_corresponding":false},{"id":272970,"name":"Nia Kyritsis","orcid":null,"position":5,"is_corresponding":false},{"id":562980,"name":"Yiwen Zhang","orcid":"0000-0003-4883-0743","position":6,"is_corresponding":false},{"id":563896,"name":"Nicole Manfredonia","orcid":null,"position":7,"is_corresponding":false},{"id":563897,"name":"Rachael Judson","orcid":null,"position":8,"is_corresponding":false},{"id":271430,"name":"Huan Chen","orcid":"0000-0002-6487-7923","position":9,"is_corresponding":false},{"id":563898,"name":"Kerstin Johnson","orcid":null,"position":10,"is_corresponding":false},{"id":554146,"name":"Sherry Lin","orcid":"0000-0002-1275-8391","position":11,"is_corresponding":false},{"id":271434,"name":"Zhaoqing Ba","orcid":"0000-0002-8431-5469","position":12,"is_corresponding":false},{"id":43604,"name":"A. Conte","orcid":"0000-0003-2719-0994","position":13,"is_corresponding":false},{"id":554147,"name":"Rafael Casellas","orcid":"0000-0001-9282-2287","position":14,"is_corresponding":false},{"id":201746,"name":"Cheng-Sheng Lee","orcid":"0000-0002-0765-2410","position":15,"is_corresponding":false},{"id":271435,"name":"Frederick W. Alt","orcid":"0000-0002-0583-1271","position":16,"is_corresponding":false},{"id":562977,"name":"Hai‐Qiang Dai","orcid":"0000-0003-4337-9770","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-18T23:14:51.076430Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}