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Series GSE140635 Query DataSets for GSE140635
Status Public on Jan 01, 2020
Title Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [END-seq]
Organism Mus musculus
Experiment type Other
Summary During V(D)J recombination RAG proteins introduce DNA double strand breaks (DSBs) adjacent to conserved recombination signal sequences (RSS) that contain either 12- or 23-nucleotide spacer regions. Coordinated cleavage following the “12/23” rule predicts that DSBs at variable (V) gene segments should not exceed the level of breakage at joining (J) segments, thereby ensuring that V regions do not engage in undesirable recombination events with one another. Here we report abundant RAG dependent DSBs at a multitude of V gene segments within the Ig locus independent of V-J rearrangement. We discover that a large fraction of V gene segments are flanked not only by a bone-fide 12 spacer, but also an overlapping, 23 spacer flipped RSS. These compatible pairs of RSS mediate recombination and deletion inside the V cluster even in the complete absence of J gene segments, and support a novel recombination center (RC) independent of the conventional J-centered RC. We propose a model that explains V gene segment usage by taking into account not only the probability of V-to-J rearrangement but also the surprisingly frequent, evolutionarily conserved intra-V cluster recombination events. These findings shed light on the diverse molecular strategies that shape the primary antigen receptor repertoires.
Overall design END-seq profile in abelson-transformed pre-B cells, primary bone marrow pre-B cells, and thymocytes.
Contributor(s) Shindoa K, Maman Y, Canela A, Shchatz DG, Livak F, Nussenzweig A
Citation(s) 31875554
Submission date Nov 18, 2019
Last update date Jul 02, 2021
Contact name Yaakov Maman
Organization name Bar-Ilan University
Department Azrieli Faculty of Medicine
Lab Genome Instability & Cancer
Street address Henrietta Szold 8
City Safed
ZIP/Postal code 1311502
Country Israel
Platforms (1)
GPL21626 NextSeq 550 (Mus musculus)
Samples (19)
GSM4176056 END_seq_PB_WT_REP1
GSM4176057 END_seq_PB_WT_REP2
GSM4176058 END_seq_PB_WT_REP3
This SubSeries is part of SuperSeries:
GSE140677 Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire
BioProject PRJNA590463
SRA SRP230614

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Supplementary file Size Download File type/resource
GSE140635_RAW.tar 1.3 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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