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Ensuring an equal playing field for antigen receptor loci variable regions.

Murre C - J. Exp. Med. (2015)

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Affiliation: University of California, San Diego cmurre@ucsd.edu.

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During the developmental progression of lymphoid progenitors, antigen receptor loci are assembled from variable (V), diversity (D), and joining (J) gene segments... In precursor B cells, the immunoglobulin heavy chain (Igh) locus undergoes ordered gene segment rearrangement with DHJH joining preceding VH to DHJH rearrangement... The ordered rearrangement of the Igh locus is controlled by an insulator element, characterized by two CTCF binding sites, named the intergenic control region 1 (IGCR1), located between the VH and DHJH region... They identify two elements within the insulator: a distally located high affinity CTCF biding site and a more proximal region characterized by relatively weak CTCF binding... They found that the most distally located CTCF-containing element functions as an anchor to promote looping of distal Vβ regions to the DβJβ region, essentially promoting locus contraction... The second element, located most proximally to the DβJβ region, acts as a barrier to prevent the spreading of active chromatin associated with the DβJβ region into the CTCF anchor... However, removal of the proximal element interferes with the ability of the distal element to promote locus contraction... Thus, these findings point to a separation of function for binding sites associated with insulator elements: anchors that promote long-range contraction must be protected from transcriptionally active chromatin by boundary elements... It will be particularly interesting to examine whether and how trajectories adopted by the V and DJ regions across antigen receptor loci are controlled by the insulator-anchoring elements and how alterations in the paths taken by the chromatin fibers affect genomic encounters... Finally, the regulation of long-range genomic interactions—as described by this group and others—is not likely to be restricted to antigen receptor loci only... Rather, these studies will very likely serve as a paradigm for locus region encounters involving regulatory elements across genomes of both animal and plant kingdoms.

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An anchor and a barrier separate the Vβ regions from the DJ clusters and ensure the generation of a diverse TCRβ repertoire.
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fig2: An anchor and a barrier separate the Vβ regions from the DJ clusters and ensure the generation of a diverse TCRβ repertoire.


Ensuring an equal playing field for antigen receptor loci variable regions.

Murre C - J. Exp. Med. (2015)

An anchor and a barrier separate the Vβ regions from the DJ clusters and ensure the generation of a diverse TCRβ repertoire.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4291535&req=5

fig2: An anchor and a barrier separate the Vβ regions from the DJ clusters and ensure the generation of a diverse TCRβ repertoire.

View Article: PubMed Central - HTML - PubMed

Affiliation: University of California, San Diego cmurre@ucsd.edu.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

During the developmental progression of lymphoid progenitors, antigen receptor loci are assembled from variable (V), diversity (D), and joining (J) gene segments... In precursor B cells, the immunoglobulin heavy chain (Igh) locus undergoes ordered gene segment rearrangement with DHJH joining preceding VH to DHJH rearrangement... The ordered rearrangement of the Igh locus is controlled by an insulator element, characterized by two CTCF binding sites, named the intergenic control region 1 (IGCR1), located between the VH and DHJH region... They identify two elements within the insulator: a distally located high affinity CTCF biding site and a more proximal region characterized by relatively weak CTCF binding... They found that the most distally located CTCF-containing element functions as an anchor to promote looping of distal Vβ regions to the DβJβ region, essentially promoting locus contraction... The second element, located most proximally to the DβJβ region, acts as a barrier to prevent the spreading of active chromatin associated with the DβJβ region into the CTCF anchor... However, removal of the proximal element interferes with the ability of the distal element to promote locus contraction... Thus, these findings point to a separation of function for binding sites associated with insulator elements: anchors that promote long-range contraction must be protected from transcriptionally active chromatin by boundary elements... It will be particularly interesting to examine whether and how trajectories adopted by the V and DJ regions across antigen receptor loci are controlled by the insulator-anchoring elements and how alterations in the paths taken by the chromatin fibers affect genomic encounters... Finally, the regulation of long-range genomic interactions—as described by this group and others—is not likely to be restricted to antigen receptor loci only... Rather, these studies will very likely serve as a paradigm for locus region encounters involving regulatory elements across genomes of both animal and plant kingdoms.

Show MeSH