Functional long-range interactions of the IgH 3' enhancers with the bcl-2 promoter region in t(14;18) lymphoma cells

Oncogene. 2008 Dec 4;27(53):6720-8. doi: 10.1038/onc.2008.286. Epub 2008 Aug 11.


To better understand the mechanisms underlying the role of the immunoglobulin heavy-chain gene (IgH) 3' enhancers on bcl-2 transcriptional deregulation in t(14;18) lymphoma, we characterized the physical interactions of the IgH 3' enhancer region with the bcl-2 promoters. Using the chromosome conformation capture technique, we found that the IgH 3' enhancers physically interact with the bcl-2 promoter region over a 350 kb genomic region in t(14;18) lymphoma cells. No interactions of the bcl-2 promoter region with sequences distant to the IgH enhancers were observed. The physical interactions of the IgH enhancers with the bcl-2 5' region are functionally involved in the transcriptional control of bcl-2. The histone deacetylase inhibitor, trichostatin A, repressed bcl-2 transcription and decreased the IgH enhancer-bcl-2 promoter region interactions. We showed by chromatin immunoprecipitation assay and small interference RNA transfection studies that the POU2 family transcription factor Oct-2 and its cofactor Bob-1 have an important function in mediating the IgH enhancer-bcl-2 promoter region interactions. This study reveals a new aspect of the regulatory role of the IgH 3' enhancers on bcl-2 transcription in t(14;18) lymphomas.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line, Tumor
  • Chromosomes, Human, Pair 14 / genetics
  • Chromosomes, Human, Pair 14 / metabolism
  • Chromosomes, Human, Pair 18 / genetics
  • Chromosomes, Human, Pair 18 / metabolism
  • Enhancer Elements, Genetic / genetics*
  • Enzyme Inhibitors / pharmacology
  • Genes, bcl-2 / genetics*
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Humans
  • Hydroxamic Acids / pharmacology
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Heavy Chains / metabolism
  • Lymphoma / genetics*
  • Lymphoma / metabolism
  • Octamer Transcription Factor-2 / genetics
  • Octamer Transcription Factor-2 / metabolism
  • Promoter Regions, Genetic / genetics*
  • RNA, Small Interfering / genetics
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics*
  • Translocation, Genetic


  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Immunoglobulin Heavy Chains
  • Octamer Transcription Factor-2
  • POU2AF1 protein, human
  • RNA, Small Interfering
  • Trans-Activators
  • trichostatin A
  • Histone Deacetylases