|
| Status |
Public on Jan 01, 2020 |
| Title |
Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [HTGTS] |
| Organisms |
Homo sapiens; 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 |
HTGTS profile in abelson-transformed pre-B cells, primary splenic B cells, bone marrow B cells, and human PBMC B cells.
|
| |
|
| Contributor(s) |
Shindoa K, Maman Y, Canela A, Shchatz DG, Livak F, Nussenzweig A |
| Citation(s) |
31875554 |
| |
| Submission date |
Nov 19, 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 (2) |
|
| Samples (41)
|
|
| This SubSeries is part of SuperSeries: |
| GSE140677 |
Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire |
|
| Relations |
| BioProject |
PRJNA590491 |
| SRA |
SRP230629 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE140672_HTGTS_BMPB_VK1_117.tlx.txt.gz |
546.8 Kb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PBMC_B_JK1.tlx.txt.gz |
1022.8 Kb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PBMC_B_VK2_28.tlx.txt.gz |
479.4 Kb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PBMC_B_VK3_20.tlx.txt.gz |
401.7 Kb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PB_JK1_WT.tlx.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PB_VK1_117_ART_clone1.tlx.txt.gz |
7.7 Kb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PB_VK1_117_ART_clone2.tlx.txt.gz |
7.2 Kb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PB_VK1_117_CRISPR.tlx.txt.gz |
1.7 Mb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PB_VK1_117_CRISPR_NO_STI.tlx.txt.gz |
396.6 Kb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PB_VK1_117_DELJK.tlx.txt.gz |
3.0 Mb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PB_VK1_117_LIG4.tlx.txt.gz |
10.4 Kb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PB_VK1_117_RAG1.tlx.txt.gz |
291.9 Kb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PB_VK1_117_WT.tlx.txt.gz |
3.1 Mb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PB_VK8_34_DELJK.tlx.txt.gz |
352.5 Kb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_PB_VK8_34_WT.tlx.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_Spl_B_JK1.tlx.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE140672_HTGTS_Spl_B_VK1_117.tlx.txt.gz |
275.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
Less...
More...