Browse
Submit Data
Databases
API
Help

Dataset Information

30 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire.

ABSTRACT: During V(D)J recombination, RAG proteins introduce DNA double-strand breaks (DSBs) at recombination signal sequences (RSSs) that contain either 12- or 23-nt spacer regions. Coordinated 12/23 cleavage predicts that DSBs at variable (V) gene segments should equal the level of breakage at joining (J) segments. Contrary to this, here we report abundant RAG-dependent DSBs at multiple Vκ gene segments independent of V-J rearrangement. We find that a large fraction of Vκ gene segments are flanked not only by a bone-fide 12 spacer but also an overlapping, 23-spacer flipped RSS. These compatible pairs of RSSs mediate recombination and deletion inside the Vκ cluster even in the complete absence of Jκ gene segments and support a V(D)J recombination center (RC) independent of the conventional Jκ-centered RC. We propose an improved model of Vκ-Jκ repertoire formation by incorporating these surprisingly frequent, evolutionarily conserved intra-Vκ cluster recombination events.

SUBMITTER: Shinoda K

PROVIDER: S-EPMC8214342 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-01-01 | GSE140677 | GEO

Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [HTGTS]

Project description: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.

2020-01-01 | GSE140672 | GEO

Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [ChIP-seq]

2020-01-01 | GSE140655 | GEO

Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [END-seq]

2020-01-01 | GSE140635 | GEO

Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire

Project description:Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire

| PRJNA590489 | ENA

Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [HTGTS]

Project description:Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [HTGTS]

| PRJNA590491 | ENA

Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [ChIP-seq]

Project description:Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [ChIP-seq]

| PRJNA590470 | ENA

Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [END-seq]

Project description:Intra-Vk Cluster Recombination Shapes the Ig Kappa Locus Repertoire [END-seq]

| PRJNA590463 | ENA

Vκ gene repertoire and locus contraction are specified by critical DNase I hypersensitive sites within the Vκ-Jκ intervening region.

Project description:The processes of Ig gene locus contraction and looping during V(D)J-recombination are essential for creating a diverse Ab repertoire. However, no cis-acting sequence that plays a major role in specifying locus contraction has been uncovered within the Igκ gene locus. In this article, we demonstrate that a 650-bp sequence corresponding to DNase I hypersensitive sites HS1-2 within the mouse Igκ gene V-J intervening region binds CCCTC-binding factor and specifies locus contraction and long-range Vκ gene usage spanning 3.2 Mb in pre-B cells. We call this novel element Cer (for "contracting element for recombination"). Targeted deletion of Cer caused markedly increased proximal and greatly diminished upstream Vκ gene usage, higher allele usage, more splenic Igκ(+) B cells, and nonlineage-specific Igκ rearrangement in T cells. Relative to wild-type mice, Cer-deletion mice exhibited similar levels of Vκ gene germline transcription and H3K4me3 epigenetic marks but displayed a dramatic decrease in locus contraction in pre-B cells. Thus, our studies demonstrate that DNase I hypersensitive sites HS1-2 within the Vκ-Jκ intervening region are essential for controlling locus contraction and creating a diverse Ab repertoire.

| S-EPMC3563863 | biostudies-literature

A multifunctional element in the mouse Ig? locus that specifies repertoire and Ig loci subnuclear location.

Project description:Nonbiased V gene usage for V(D)J joining is essential for providing an optimal immune system, but no cis-acting sequence with this function has been uncovered. We previously identified a recombination silencer and heterochromatin targeting element in the V?-J? intervening sequence of germline Ig? transgenes, which we termed Sis. We now have generated Sis knockout mice in the endogenous locus. Intriguingly, Sis(-/-) mice exhibit a skewed Ig? repertoire with markedly decreased distal and enhanced proximal V? gene usage for primary rearrangement, which is associated with reduced occupancy of Ikaros and CCCTC-binding factor in the V?-J? intervening sequence in pre-B cells, proteins believed to be responsible for dampening the recombination of nearby V? genes and altering higher-order chromatin looping. Furthermore, monoallelic heterochromatin localization is significantly reduced in Sis(-/-) mice for Ig? in cis and IgH loci in trans in pre-B cells. Because Sis(-/-) mice still allelically excluded Ig? and IgH loci and still exhibited IgL isotype exclusion, we concluded that stable localization at pericentromeric heterochromatin is neither necessary nor sufficient for the establishment or maintenance of allelic exclusion. Hence, Sis is a novel multifunctional element that specifies repertoire and heterochromatin localization to Ig genes.

| S-EPMC3080443 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data