Conserved kappa B element located downstream of the tumor necrosis factor alpha gene: distinct NF-kappa B binding pattern and enhancer activity in LPS activated murine macrophages.
Transcriptional activation of various genes by lipopolysaccharide (LPS) is known to be mediated, at least in part, by the NF-kappa B/Rel family of transcription factors. We have identified a novel kappa B element located immediately downstream of the TNF-alpha gene that is conserved together with it...
| Egile Nagusiak: | , , , , |
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| Formatua: | Journal article |
| Hizkuntza: | English |
| Argitaratua: |
1995
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| _version_ | 1826270264008114176 |
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| author | Kuprash, D Udalova, I Turetskaya, R Rice, N Nedospasov, SA |
| author_facet | Kuprash, D Udalova, I Turetskaya, R Rice, N Nedospasov, SA |
| author_sort | Kuprash, D |
| collection | OXFORD |
| description | Transcriptional activation of various genes by lipopolysaccharide (LPS) is known to be mediated, at least in part, by the NF-kappa B/Rel family of transcription factors. We have identified a novel kappa B element located immediately downstream of the TNF-alpha gene that is conserved together with its flanking sequences across species lines and can act as an LPS-responsive enhancer for reporter gene constructs driven by the minimal TNF promoter. In extracts from activated murine macrophages and macrophage cell lines this element binds several non-canonical NF-kappa B/Rel complexes, in addition to p50 (NFKB1) homodimer and p50-p65 (NKFB1-RelA) heterodimer. Combination of high-resolution electrophoretic mobility shift assays (EMSA) with monospecific antibodies and u.v.-cross-linking indicates that the prominent slow migrating complex III contain p65 homodimer and c-Rel. The appearance of complex III in EMSA parallels the translocation of p65 and c-Rel into the nucleus and occurs shortly after LPS induction. Transfection experiments with reporter constructs driven by this kappa B element indicate strong inducibility by LPS and p65, moderate inducibility by c-Rel and repression by p50. Functional activity of sandwich TNF-CAT-TNF constructs further suggests that LPS-inducible transcriptional activation of the TNF gene in murine macrophages may be partly mediated by a downstream enhancer. |
| first_indexed | 2024-03-06T21:38:07Z |
| format | Journal article |
| id | oxford-uuid:46f8387f-c645-43c7-b60b-bcdb1e8f3976 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:38:07Z |
| publishDate | 1995 |
| record_format | dspace |
| spelling | oxford-uuid:46f8387f-c645-43c7-b60b-bcdb1e8f39762022-03-26T15:17:07ZConserved kappa B element located downstream of the tumor necrosis factor alpha gene: distinct NF-kappa B binding pattern and enhancer activity in LPS activated murine macrophages.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:46f8387f-c645-43c7-b60b-bcdb1e8f3976EnglishSymplectic Elements at Oxford1995Kuprash, DUdalova, ITuretskaya, RRice, NNedospasov, SATranscriptional activation of various genes by lipopolysaccharide (LPS) is known to be mediated, at least in part, by the NF-kappa B/Rel family of transcription factors. We have identified a novel kappa B element located immediately downstream of the TNF-alpha gene that is conserved together with its flanking sequences across species lines and can act as an LPS-responsive enhancer for reporter gene constructs driven by the minimal TNF promoter. In extracts from activated murine macrophages and macrophage cell lines this element binds several non-canonical NF-kappa B/Rel complexes, in addition to p50 (NFKB1) homodimer and p50-p65 (NKFB1-RelA) heterodimer. Combination of high-resolution electrophoretic mobility shift assays (EMSA) with monospecific antibodies and u.v.-cross-linking indicates that the prominent slow migrating complex III contain p65 homodimer and c-Rel. The appearance of complex III in EMSA parallels the translocation of p65 and c-Rel into the nucleus and occurs shortly after LPS induction. Transfection experiments with reporter constructs driven by this kappa B element indicate strong inducibility by LPS and p65, moderate inducibility by c-Rel and repression by p50. Functional activity of sandwich TNF-CAT-TNF constructs further suggests that LPS-inducible transcriptional activation of the TNF gene in murine macrophages may be partly mediated by a downstream enhancer. |
| spellingShingle | Kuprash, D Udalova, I Turetskaya, R Rice, N Nedospasov, SA Conserved kappa B element located downstream of the tumor necrosis factor alpha gene: distinct NF-kappa B binding pattern and enhancer activity in LPS activated murine macrophages. |
| title | Conserved kappa B element located downstream of the tumor necrosis factor alpha gene: distinct NF-kappa B binding pattern and enhancer activity in LPS activated murine macrophages. |
| title_full | Conserved kappa B element located downstream of the tumor necrosis factor alpha gene: distinct NF-kappa B binding pattern and enhancer activity in LPS activated murine macrophages. |
| title_fullStr | Conserved kappa B element located downstream of the tumor necrosis factor alpha gene: distinct NF-kappa B binding pattern and enhancer activity in LPS activated murine macrophages. |
| title_full_unstemmed | Conserved kappa B element located downstream of the tumor necrosis factor alpha gene: distinct NF-kappa B binding pattern and enhancer activity in LPS activated murine macrophages. |
| title_short | Conserved kappa B element located downstream of the tumor necrosis factor alpha gene: distinct NF-kappa B binding pattern and enhancer activity in LPS activated murine macrophages. |
| title_sort | conserved kappa b element located downstream of the tumor necrosis factor alpha gene distinct nf kappa b binding pattern and enhancer activity in lps activated murine macrophages |
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