Spatial Regulation of V–(D)J Recombination at Antigen Receptor Loci

Ebert, Anja; Hill, Louisa; Busslinger, Meinrad

doi:10.1016/bs.ai.2015.07.006

Cited by 49 publications

(39 citation statements)

References 78 publications

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“…CTCF can perform other architectural functions, such as bringing together widely separated DNA sequences during V(D)J (Medvedovic et al 2013;Ebert et al 2015;Gerasimova et al 2015;Lin et al 2015;Narendra et al 2015) and class switch (Birshtein 2012) recombination. One class of CTCF sites that does not fit neatly into this picture has been found in the α-satellite repeats of pericentromeric regions.…”

Section: Other Roles For Ctcfmentioning

confidence: 99%

CTCF: making the right connections

2016

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The role of the zinc finger protein CTCF in organizing the genome within the nucleus is now well established. Widely separated sites on DNA, occupied by both CTCF and the cohesin complex, make physical contacts that create large loop domains. Additional contacts between loci within those domains, often also mediated by CTCF, tend to be favored over contacts between loci in different domains. A large number of studies during the past 2 years have addressed the questions: How are these loops generated? What are the effects of disrupting them? Are there rules governing large-scale genome organization? It now appears that the strongest and evolutionarily most conserved of these CTCF interactions have specific rules for the orientation of the paired CTCF sites, implying the existence of a nonequilibrium mechanism of generation. Recent experiments that invert, delete, or inactivate one of a mating CTCF pair result in major changes in patterns of organization and gene expression in the surrounding regions. What remain to be determined are the detailed molecular mechanisms for re-establishing loop domains and maintaining them after replication and mitosis. As recently published data show, some mechanisms may involve interactions with noncoding RNAs as well as protein cofactors. Many CTCF sites are also involved in other functions such as modulation of RNA splicing and specific regulation of gene expression, and the relationship between these activities and loop formation is another unanswered question that should keep investigators occupied for some time.

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Section: Other Roles For Ctcfmentioning

confidence: 99%

CTCF: making the right connections

2016

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“…Third, distal V H genes are located up to 1·1 Mb away from the 5′‐most D H gene ( DFL16.1 ). Therefore, the pro‐B cell‐specific compaction of the Igh locus is responsible for bringing the distal V H genes into proximity with the rearranged DJ H junction, which critically depends on the interaction between B‐cell commitment factor Pax5 and Pax5‐associated intergenic repeat (PAIR) elements in the distal V H region . It is necessary to analyse the influence of DJ H recombination on the accessibility of PAIR elements to reinforce the interaction between Pax5 and PAIR elements.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the pro-B cellspecific compaction of the Igh locus is responsible for bringing the distal V H genes into proximity with the rearranged DJ H junction, which critically depends on the interaction between B-cell commitment factor Pax5 and Pax5associated intergenic repeat (PAIR) elements in the distal V H region. [22][23][24][25][26] It is necessary to analyse the influence of DJ H recombination on the accessibility of PAIR elements to reinforce the interaction between Pax5 and PAIR elements. Fourth, binding of RAG to D H and J H gene segments has previously been characterized in the germline Igh locus.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic modifications of the V_H region after DJ_H recombination in Pro‐B cells

Dong

Zhao

et al. 2017

Immunology

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The variable region of murine immunoglobulin heavy chain (Igh) is assembled by sequential D -J and V -DJ recombination. The accessibility of the Igh locus determines the order of rearrangement. Because of the large number of V genes and the lack of a suitable model, the epigenetic modifications of V genes after DJ recombination have not previously been characterized. Here, we employed two v-Abl pro-B cell lines, in which the Igh locus is in germline and DJ -recombined configurations, respectively. The DJ junction displays the characteristics of a recombination centre, such as high levels of activation-associated histone modifications and recombination-activating gene protein (RAG) binding in DJ -rearranged pro-B cells, which extend the recombination centre model proposed for the germline Igh locus. The different domains of the V region have distinct epigenetic characteristics after DJ recombination. Distal V genes have higher levels of active histone modifications, germline transcription and Pax5 binding, and good quality recombination signal sequences. Proximal V genes are relatively close to the DJ recombination centre, which partially compensates for the low levels of the above active epigenetic modifications. DJ recombination centre might serve as a cis-acting element to regulate the accessibility of the V region. Furthermore, we demonstrate that RAG weakly binds to functional V genes, which is the first detailed assessment of RAG dynamic binding to V genes. We provide a way for V -DJ recombination in which the V gene is brought into close proximity with the DJ recombination centre for RAG binding by a Pax5-dependent chromosomal compaction event, and held in this position for subsequent cleavage and V -DJ joining.

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“…A diverse antigen receptor repertoire is key to adaptive immunity. This diversity relies on the recombination of three pools of gene segments within all antigen receptor loci . These pools are known as variable (V), diversity (D) and joining (J).…”

mentioning

confidence: 99%

“…This diversity relies on the recombination of three pools of gene segments within all antigen receptor loci. [1][2][3][4] These pools are known as variable (V), diversity (D) and joining (J). Each antigen receptor loci contains a different number and arrangement of the gene segments.…”

mentioning

confidence: 99%

Kinks in the chain: examining recombination‐activating gene scanning during V(D)J recombination

Johanson

Allan

2019

Immunol Cell Biol

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Spatial Regulation of V–(D)J Recombination at Antigen Receptor Loci

Cited by 49 publications

References 78 publications

CTCF: making the right connections

CTCF: making the right connections

Epigenetic modifications of the V_H region after DJ_H recombination in Pro‐B cells

Kinks in the chain: examining recombination‐activating gene scanning during V(D)J recombination

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Spatial Regulation of V–(D)J Recombination at Antigen Receptor Loci

Cited by 49 publications

References 78 publications

CTCF: making the right connections

CTCF: making the right connections

Epigenetic modifications of the VH region after DJH recombination in Pro‐B cells

Kinks in the chain: examining recombination‐activating gene scanning during V(D)J recombination

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Epigenetic modifications of the V_H region after DJ_H recombination in Pro‐B cells