{"doi":"10.1101/2020.01.01.891473","title":"CTCF orchestrates long-range cohesin-driven V(D)J recombinational scanning","abstract":"Abstract RAG endonuclease initiates V(D)J recombination in progenitor (pro)-B cells 1 . Upon binding a recombination center (RC)-based J H , RAG scans upstream chromatin via loop extrusion, potentially mediated by cohesin 2–10 , to locate Ds and assemble a DJ H -based RC 11 . CTCF looping factor-bound elements (CBEs) within IGCR1 upstream of Ds impede RAG-scanning 12–15 ; but their inactivation allows scanning to proximal V H s where additional CBEs activate rearrangement and impede scanning any further upstream 15, 16 . Distal V H utilization is thought to involve diffusional RC access following large-scale Igh locus contraction 17–23 . Here, we test the potential of linear RAG-scanning to mediate distal V H usage in G1-arrested, v-Abl- pro-B cell lines 24, 25 , which undergo robust D-to-J H but little V H -to-DJ H rearrangements, presumably due to lack of locus contraction 11, 15 . Through an auxin-inducible approach 26, 27 , we degrade the cohesin-component Rad21 4, 7, 27 or CTCF 7, 9 in these G1-arrested lines, which maintain substantial viability throughout four-day experiments. Rad21 degradation eliminated all V(D)J recombination and RAG-scanning-associated interactions, except RC-located DQ52-to-J H joining in which synapsis occurs by diffusion 11 . Remarkably, while CTCF degradation suppressed most CBE-based chromatin interactions, it promoted robust RC interactions with, and robust V H -to-DJ H joining of, distal V H s, with patterns similar to those of “locus-contracted” primary pro-B cells. Thus, down-modulation of CTCF-bound scanning-impediment activity promotes cohesin-driven RAG-scanning across the 2.7Mb Igh locus.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":119351,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"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":555064,"name":"Jiangman Lou","orcid":null,"position":1,"is_corresponding":false},{"id":555065,"name":"Edward W. Dring","orcid":null,"position":2,"is_corresponding":false},{"id":33696,"name":"Adam Yongxin Ye","orcid":"0000-0002-1542-0740","position":3,"is_corresponding":false},{"id":554146,"name":"Sherry Lin","orcid":"0000-0002-1275-8391","position":4,"is_corresponding":false},{"id":555066,"name":"Suvi Jain","orcid":null,"position":5,"is_corresponding":false},{"id":555067,"name":"Kyong-Rim Kieffer-Kwon","orcid":null,"position":6,"is_corresponding":false},{"id":554147,"name":"Rafael Casellas","orcid":"0000-0001-9282-2287","position":7,"is_corresponding":false},{"id":271435,"name":"Frederick W. Alt","orcid":"0000-0002-0583-1271","position":8,"is_corresponding":false},{"id":271434,"name":"Zhaoqing Ba","orcid":"0000-0002-8431-5469","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T23:14:08.313144Z","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":[]}