Aberrant regulation of the IgH 3' enhancer by c-myc in plasmacytoma cells.
The identification of enhancers at the 3' end of the IgH locus has prompted a re-evaluation of the regulation of Ig gene expression. Moreover, these elements may provide a possible explanation as to how the c-myc oncogene becomes dysregulated upon translocation into the IgH locus with the IgH intragenic enhancer on the reciprocal chromosome. These 3' enhancers have also been shown to redirect promoter utilization on c-myc reporter gene constructs in transient transfection experiments. This region of the locus also contains the B cell specific IgH 3' enhancer. This temporally regulated enhancer has been implicated in the mechanisms that control class switch recombination. Here we demonstrate that overexpression of the c-myc protein in mouse plasmacytoma cells (MPC-11) and HeLa cells can transcriptionally upregulate a reporter gene construct driven by a subregion (domain C) of the IgH 3' enhancer. Domain C contains a functional dual symmetry E-box motif, CACGTG. The DNA binding experiments demonstrate that USF was the major factor interacting with this motif. Based on these observations, we speculate that the c-myc protein may upregulate expression of translocated c-myc in mouse plasmacytomas possibly via an USF-binding E-box motif in the IgH 3' enhancer.
Arulampalam
V
V
Center for Biotechnology, Karolinska Institute, Huddinge, Sweden.
Grant
P
P
Poellinger
L
L
Pettersson
S
S
D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D016259:Genes, myc / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010954:Plasmacytoma / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured; D051720:Upstream Stimulatory Factors
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; C069203:TFE3 protein, human; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse