Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 210 75

The B-lymphocyte-specific activity of the immunoglobulin mu heavy-chain gene enhancer has been attributed to the octamer motif (ATTTGCAT) present within the enhancer that binds a B-cell-specific factor designated NF-A2/OTF-2. However, significant residual enhancer activity even after deletion of this element has suggested the presence of a second critical functional determinant. We have used deletion and mutational analyses to define an element, microB (TTTGGGGAA), that is essential for B-cell-specific enhancer activity in S194 myeloma cells in the absence of the octamer. Transfection analysis in a panel of lymphoid cell lines suggests that the presence of either microB or octamer leads to considerable enhancer activity in cell lines representing later stages of B-cell differentiation, whereas both elements are needed for function in cell lines representing earlier stages. Furthermore, in contrast to the results in pre-B-cell lines, both microB and octamer elements function independently in certain T-cell lines in which the mu enhancer is active.
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PMID:Complex regulation of the immunoglobulin mu heavy-chain gene enhancer: microB, a new determinant of enhancer function. 211 46

We have shown previously that genes activated by the immunoglobulin heavy chain (IgH) enhancer or promoter in mouse myeloma cells are extinguished upon fusion of the myeloma with a mouse T cell lymphoma. Here we show that the conserved octamer sequence shared by the IgH enhancer and promoter, when multimerized to form a tissue-specific enhancer, can also render a gene extinguishable under the same experimental conditions. Extinction, however, is not correlated with either absence of the tissue-specific transcription factor OTF-2 or loss of its ability to bind the octamer sequence. It was also found that extinction mediated by the IgH enhancer is dominant to transcriptional activation by the SV40 enhancer. We propose, therefore, that the T cell-negative regulator responsible for IgH gene extinction does not simply prevent IgH enhancer activation but interferes with gene expression more directly, perhaps by disrupting the transcription complex established as a result of tissue-specific enhancer activation.
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PMID:Role of the octamer motif in hybrid cell extinction of immunoglobulin gene expression: extinction is dominant in a two enhancer system. 254 24