Home LiteratureArticle Details
PMID: 18423198 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The 3D structure of the immunoglobulin heavy-chain locus: implications for long-range genomic interactions.

Cell ·Vol. 133 ·No. 2 ·2008-04-18 ·Pages 265-79

Jhunjhunwala S, van Zelm MC, Peak MM, Cutchin S, Riblet R, van Dongen JJ, Grosveld FG, Knoch TA, Murre C

Abstract

The immunoglobulin heavy-chain (Igh) locus is organized into distinct regions that contain multiple variable (V(H)), diversity (D(H)), joining (J(H)) and constant (C(H)) 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 V(H), D(H), J(H), and C(H) elements, showed compartmentalization and striking conformational changes involving V(H) and D(H)-J(H) elements during early B cell development. In pro-B cells, the entire repertoire of V(H) regions (2 Mbp) appeared to have merged and juxtaposed to the D(H) elements, mechanistically permitting long-range genomic interactions to occur with relatively high frequency.

MeSH Terms
Animals B-Lymphocytes/chemistry,metabolism Cell Lineage Cells, Cultured Genes, Immunoglobulin Heavy Chain Mice Mice, Inbred C57BL Models, Molecular Nucleic Acid Conformation VDJ Exons
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Jhunjhunwala Suchit
Division of Biological Sciences, 0377, University of California, San Diego, La Jolla, CA 92093, USA.
van Zelm Menno C
Peak Mandy M
Cutchin Steve
Riblet Roy
van Dongen Jacques J M
Grosveld Frank G
Knoch Tobias A
Murre Cornelis
References (31)
31 references, click to expand
  1. Ordered rearrangement of immunoglobulin heavy chain variable region segments.
    EMBO J. 1984 Jun;3(6):1209-19 PMID: 6086308
  2. Biased expression of JH-proximal VH genes occurs in the newly generated repertoire of neonatal and adult mice.
    J Exp Med. 1990 Mar 1;171(3):843-59 PMID: 2261012
  3. A transcriptional enhancer whose function imposes a requirement that proteins track along DNA.
    Science. 1992 May 29;256(5061):1298-303 PMID: 1598572
  4. Spatial preservation of nuclear chromatin architecture during three-dimensional fluorescence in situ hybridization (3D-FISH).
    Exp Cell Res. 2002 May 15;276(1):10-23 PMID: 11978004
  5. Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines.
    Nature. 1984 Oct 25-31;311(5988):727-33 PMID: 6092962
  6. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences.
    Cell. 1981 Dec;27(2 Pt 1):299-308 PMID: 6277502
  7. The bacterial enhancer-binding protein NtrC as a molecular machine.
    Cold Spring Harb Symp Quant Biol. 1998;63:157-66 PMID: 10384279
  8. Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene.
    Genes Dev. 2004 Feb 15;18(4):411-22 PMID: 15004008
  9. Individual V(H) promoters vary in strength, but the frequency of rearrangement of those V(H) genes does not correlate with promoter strength nor enhancer-independence.
    Mol Immunol. 2000 Jan-Feb;37(1-2):29-39 PMID: 10781833
  10. Chromosome territories, nuclear architecture and gene regulation in mammalian cells.
    Nat Rev Genet. 2001 Apr;2(4):292-301 PMID: 11283701
  11. High-resolution physical mapping of human 5q31-q33 using three methods: radiation hybrid mapping, interphase fluorescence in situ hybridization, and pulsed-field gel electrophoresis.
    Genomics. 1994 Nov 15;24(2):395-8 PMID: 7698768
  12. Biochemistry of V(D)J recombination.
    Curr Top Microbiol Immunol. 2005;290:49-85 PMID: 16480039
  13. Long-range chromatin regulatory interactions in vivo.
    Nat Genet. 2002 Dec;32(4):623-6 PMID: 12426570
  14. Mapping of human chromosome Xq28 by two-color fluorescence in situ hybridization of DNA sequences to interphase cell nuclei.
    Am J Hum Genet. 1991 Jan;48(1):1-15 PMID: 1985451
  15. Evidence for the organization of chromatin in megabase pair-sized loops arranged along a random walk path in the human G0/G1 interphase nucleus.
    J Cell Biol. 1995 Sep;130(6):1239-49 PMID: 7559748
  16. Locus 'decontraction' and centromeric recruitment contribute to allelic exclusion of the immunoglobulin heavy-chain gene.
    Nat Immunol. 2005 Jan;6(1):31-41 PMID: 15580273
  17. Most peripheral B cells in mice are ligand selected.
    J Exp Med. 1991 Jun 1;173(6):1357-71 PMID: 1903427
  18. Visualization of looping involving the immunoglobulin heavy-chain locus in developing B cells.
    Genes Dev. 2005 Feb 1;19(3):322-7 PMID: 15687256
  19. Looping and interaction between hypersensitive sites in the active beta-globin locus.
    Mol Cell. 2002 Dec;10(6):1453-65 PMID: 12504019
  20. Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent.
    Immunity. 2004 Mar;20(3):349-60 PMID: 15030778
  21. Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus.
    Annu Rev Immunol. 2006;24:541-70 PMID: 16551259
  22. Long-range compaction and flexibility of interphase chromatin in budding yeast analyzed by high-resolution imaging techniques.
    Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16495-500 PMID: 15545610
  23. A structural analysis of the role of the nuclear matrix and DNA loops in the organization of the nucleus and chromosome.
    J Cell Sci Suppl. 1984;1:123-35 PMID: 6397469
  24. A random-walk/giant-loop model for interphase chromosomes.
    Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2710-4 PMID: 7708711
  25. Higher order structure of chromosomes.
    Chromosoma. 1979 Apr 5;72(1):1-14 PMID: 456198
  26. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development.
    Science. 2002 Apr 5;296(5565):158-62 PMID: 11935030
  27. Dynamic alterations in the conformation of the Ifng gene region during T helper cell differentiation.
    Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):251-6 PMID: 14691261
  28. Fidelity of the protein structure reconstruction from inter-residue proximity constraints.
    J Phys Chem B. 2007 Jun 28;111(25):7432-8 PMID: 17542631
  29. The structure of histone-depleted metaphase chromosomes.
    Cell. 1977 Nov;12(3):817-28 PMID: 922894
  30. Long-range intrachromosomal interactions in the T helper type 2 cytokine locus.
    Nat Immunol. 2004 Oct;5(10):1017-27 PMID: 15378057
  31. The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred Igh-V genes comprise seven families of homologous genes.
    Eur J Immunol. 1984 Oct;14(10):922-30 PMID: 6092095
Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2008.03.024
Published
2008-04-18
Pages
265-79
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2771211
Subset
IM
Grants
NIAID NIH HHS · R01 AI023548-22 · United States
NIAID NIH HHS · R01 AI023548-17A1 · United States
NIAID NIH HHS · R01 AI023548-15 · United States
NIAID NIH HHS · R01 AI023548-19 · United States
NIAID NIH HHS · R01 AI023548-16 · United States
NIAID NIH HHS · R01 AI023548-21 · United States
NIAID NIH HHS · R01 AI023548-20A2 · United States
NIAID NIH HHS · R01 AI023548-18 · United States
NIAID NIH HHS · R01 AI023548-13 · United States
External Links
PubMed source DOI: 10.1016/j.cell.2008.03.024 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2