Extinction of Ig genes expression in myeloma x fibroblast somatic cell hybrids is accompanied by repression of the oct-2 gene encoding a B-cell specific transcription factor.
In most instances, fusion of differentiated cell types with fibroblasts has resulted in the extinction of differentiation-specific traits of the nonfibroblast parental cell. To explore the genetic basis of this phenomenon, we have used a series of somatic cell hybrids between myeloma cells and fibroblasts. Previous findings show that in these hybrids expression of the immunoglobulin (Ig) genes was extinguished at the transcriptional level. Our present results show that NF-kappa B transcription factor, known to be critical for kappa-chain enhancer activity, is present although in a lower amount, in the nucleus and in the cytosolic fraction of most of these hybrids (probably attached to the previously postulated I-kappa B inhibitor). In contrast, the expression of the NF-A2/OTF-2 transcription factor encoded by the oct-2 gene, which binds to the octameric motif located in the Ig promoters and heavy chain gene enhancer, is extinguished at the transcriptional level. Our data thus suggest that extinction of Ig genes expression occurs via an indirect mechanism in which a fibroblast factor suppresses transcription factor(s) which are critical for Ig transcription.
Bergman
Y
Y
Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Strich
B
B
Sharir
H
H
Ber
R
R
Laskov
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D005347:Fibroblasts / Q000276:immunology; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D006822:Hybrid Cells / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007739:L Cells / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000276:immunology; D015345:Oligonucleotide Probes; D010957:Plasmids; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics*
D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D015345:Oligonucleotide Probes; D014157:Transcription Factors