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Igh nuclear speckle association promotes V(D)J recombination
Saurabh Priyadarshi1, Khalid H Bhat1,2, Ellen B Drake1
1Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL, 60612-7344, USA.
Nature Communications
|April 20, 2026
Summary
The Igh locus
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- The positioning of the immunoglobulin heavy (Igh) locus within the nucleus is linked to V(D)J recombination.
- Mechanisms governing this nuclear positioning are not fully understood.
Purpose of the Study:
- To investigate the role of nuclear speckles (NS) in regulating Igh locus positioning and V(D)J recombination.
- To elucidate the relationship between Igh locus function and its nuclear compartmentalization.
Main Methods:
- DNA fluorescence in situ hybridization (FISH) to image Igh locus radial position.
- Knockdown of nuclear speckle constituents and drug inhibition to disrupt speckles.
- Assessing V(D)J recombination efficiency and chromatin accessibility.
Main Results:
- Deletion of VH14-2 shifts Igh alleles to the nuclear periphery and reduces V(D)J recombination.
- Igh loci associate with nuclear speckles, and this association is disrupted upon VH14-2 deletion.
- Disruption of nuclear speckles impairs Igh radial positioning and V(D)J recombination.
- VH14-2 deletion diminishes Igh transcription and VH chromatin accessibility.
Conclusions:
- Nuclear speckle association is crucial for proper Igh locus positioning and V(D)J recombination.
- Nuclear compartmentalization, mediated by nuclear speckles, influences Igh gene function and rearrangement.
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