Evidence for physical interaction between the immunoglobulin heavy chain variable region and the 3′ regulatory region

Zhongliang Ju, Sabrina A. Volpi, Rabih Hassan, Nancy Martinez, Sandra L. Giannini, Tamar Gold, Barbara K. Birshtein

Research output: Contribution to journalArticle

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Abstract

B cell-specific expression of immunoglobulin heavy chain (IgH) genes utilizes two cis regulatory regions, the intronic enhancer (Eμ), located in the JH-Cμ intron, and a complex regulatory region that lies 3′ to the IgH gene cluster, 3′ RR. We hypothesized that the 3′ RR is involved in IgH gene transcription in plasma cells via physical interaction between distal 3′ RR enhancers and target VH sequences, with loop formation by intervening DNA. In support of this hypothesis we report sequence data at DNA recombination breakpoints as evidence for loop formation preceding DNA inversion in a plasma cell line. In addition, using the chromosome conformation capture technique, physical interactions between V H and 3′ RR were analyzed directly and detected in MPC11 plasma cells and variants and normal splenic B cells but not detected in splenic T cells or in non-B cells. VH-3′ RR interactions were present in the absence of Eμ, but when the hs1,2 enhancer was replaced by a Neo R gene in a variant cell line lacking Eμ, H chain expression was lost, and interactions between VH and 3′ RR and among the 3′ RR regulators themselves were severely disrupted. In addition, the chromosome conformation capture technique detected interactions between the myc promoter and 3′ RR elements in MPC11, which like other plasmacytomas contains a reciprocal translocation between the c-myc and the IgH locus. In sum, our data support a hypothesis that cis VH-3′ RR and myc-3′ RR interactions involve physical interactions between these DNA elements.

Original languageEnglish (US)
Pages (from-to)35169-35178
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number48
DOIs
StatePublished - Nov 30 2007

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Immunoglobulin Heavy Chains
Nucleic Acid Regulatory Sequences
Immunoglobulin Heavy Chain Genes
Plasma Cells
Cells
Genes
DNA
Chromosomes
B-Lymphocytes
Plasmas
Conformations
vpr Genes
Cell Line
Plasmacytoma
Multigene Family
T-cells
Introns
Genetic Recombination
Beam plasma interactions
Transcription

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ju, Z., Volpi, S. A., Hassan, R., Martinez, N., Giannini, S. L., Gold, T., & Birshtein, B. K. (2007). Evidence for physical interaction between the immunoglobulin heavy chain variable region and the 3′ regulatory region. Journal of Biological Chemistry, 282(48), 35169-35178. https://doi.org/10.1074/jbc.M705719200

Evidence for physical interaction between the immunoglobulin heavy chain variable region and the 3′ regulatory region. / Ju, Zhongliang; Volpi, Sabrina A.; Hassan, Rabih; Martinez, Nancy; Giannini, Sandra L.; Gold, Tamar; Birshtein, Barbara K.

In: Journal of Biological Chemistry, Vol. 282, No. 48, 30.11.2007, p. 35169-35178.

Research output: Contribution to journalArticle

Ju, Z, Volpi, SA, Hassan, R, Martinez, N, Giannini, SL, Gold, T & Birshtein, BK 2007, 'Evidence for physical interaction between the immunoglobulin heavy chain variable region and the 3′ regulatory region', Journal of Biological Chemistry, vol. 282, no. 48, pp. 35169-35178. https://doi.org/10.1074/jbc.M705719200
Ju, Zhongliang ; Volpi, Sabrina A. ; Hassan, Rabih ; Martinez, Nancy ; Giannini, Sandra L. ; Gold, Tamar ; Birshtein, Barbara K. / Evidence for physical interaction between the immunoglobulin heavy chain variable region and the 3′ regulatory region. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 48. pp. 35169-35178.
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