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<p><i>Igh</i> locus positioning in the nuclear center is correlated with V to DJ recombination. However, the mechanisms that dictate radial positioning remain undefined. Deletion of the highly transcribed <i>V</i><sub><i>H</i></sub><i>14-2</i> led to reduced V to DJ rearrangements and increased locus contraction that facilitates V(D)J recombination. To reconcile these findings, we imaged <i>Igh</i> radial position by DNA fluorescence in situ hybridization and found that <i>V</i><sub><i>H</i></sub><i>14-2</i> deleted alleles locate in the nuclear periphery implying that nuclear compartmentalization may be linked to nuclear body association. We found that <i>Igh</i> loci associate with nuclear speckles (NS) and these contacts are reduced for <i>V</i><sub><i>H</i></sub><i>14-2</i> deleted alleles. Knockdown of NS constituents or treatment with a drug inhibitor led to disaggregation of speckles and impaired <i>Igh</i> radial positioning. Chemical disruption of speckles also caused reduced V to DJ recombination. <i>Igh</i> transcription and V<sub>H</sub> chromatin accessibility are diminished in <i>V</i><sub>H</sub><i>14-2</i> deleted alleles linking function to NS association.</p>

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Igh nuclear speckle association promotes V(D)J recombination

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月20日

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  • Saurabh Priyadarshi,
  • Khalid H. Bhat,
  • Ellen B. Drake,
  • Sarah Naiyer,
  • Hammad Farooq,
  • Xinyan Qu,
  • Jose F. Cantillo,
  • Xue Lei,
  • Ebru Ermis,
  • Eden Kleiman,
  • Sajad A. Bhat,
  • Andrew Koh,
  • Jie Liang,
  • Ann J. Feeney,
  • Jan H. Spille,
  • Amy L. Kenter

摘要

Igh locus positioning in the nuclear center is correlated with V to DJ recombination. However, the mechanisms that dictate radial positioning remain undefined. Deletion of the highly transcribed VH14-2 led to reduced V to DJ rearrangements and increased locus contraction that facilitates V(D)J recombination. To reconcile these findings, we imaged Igh radial position by DNA fluorescence in situ hybridization and found that VH14-2 deleted alleles locate in the nuclear periphery implying that nuclear compartmentalization may be linked to nuclear body association. We found that Igh loci associate with nuclear speckles (NS) and these contacts are reduced for VH14-2 deleted alleles. Knockdown of NS constituents or treatment with a drug inhibitor led to disaggregation of speckles and impaired Igh radial positioning. Chemical disruption of speckles also caused reduced V to DJ recombination. Igh transcription and VH chromatin accessibility are diminished in VH14-2 deleted alleles linking function to NS association.