The 3D Structure of the Immunoglobulin Heavy-Chain Locus: Implications for Long-Range Genomic Interactions

Suchit Jhunjhunwala, Menno C. van Zelm, Mandy M. Peak, Steve Cutchin, Roy Riblet, Jacques J M van Dongen, Frank G. Grosveld, Tobias A. Knoch, Cornelis Murre

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206 Citations (Scopus)

Abstract

The immunoglobulin heavy-chain (Igh) locus is organized into distinct regions that contain multiple variable (VH), diversity (DH), joining (JH) and constant (CH) coding elements. How the Igh locus is structured in 3D space is unknown. To probe the topography of the Igh locus, spatial distance distributions were determined between 12 genomic markers that span the entire Igh locus. Comparison of the distance distributions to computer simulations of alternative chromatin arrangements predicted that the Igh locus is organized into compartments containing clusters of loops separated by linkers. Trilateration and triple-point angle measurements indicated the mean relative 3D positions of the VH, DH, JH, and CH elements, showed compartmentalization and striking conformational changes involving VH and DH-JH elements during early B cell development. In pro-B cells, the entire repertoire of VH regions (2 Mbp) appeared to have merged and juxtaposed to the DH elements, mechanistically permitting long-range genomic interactions to occur with relatively high frequency.

Original languageEnglish
Pages (from-to)265-279
Number of pages15
JournalCell
Volume133
Issue number2
DOIs
Publication statusPublished - 18 Apr 2008
Externally publishedYes

Keywords

  • CELLBIO
  • DNA
  • MOLIMMUNO

Cite this

Jhunjhunwala, S., van Zelm, M. C., Peak, M. M., Cutchin, S., Riblet, R., van Dongen, J. J. M., Grosveld, F. G., Knoch, T. A., & Murre, C. (2008). The 3D Structure of the Immunoglobulin Heavy-Chain Locus: Implications for Long-Range Genomic Interactions. Cell, 133(2), 265-279. https://doi.org/10.1016/j.cell.2008.03.024