Identification of new Rel/NFκB regulatory networks by focused genome location analysis
NFκB is an inducible transcription factor that controls kinetically complex patterns of gene expression. Several studies reveal multiple pathways linking NFκB to the promotion and progression of various cancers. Despite extensive interest and characterization, many NFκB controlled genes still remain...
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todo:paper_15384101_v8_n13_p2093_DeSiervi2023-10-03T16:21:57Z Identification of new Rel/NFκB regulatory networks by focused genome location analysis De Siervi, A. De Luca, P. Moiola, C. Gueron, G. Tongbai, R. Chandramouli, G.V.R. Haggerty, C. Dzekunova, I. Petersen, D. Kawasaki, E. Whoon, J.K. Camphausen, K. Longo, D. Gardner, K. ATM ChIP/chip Ets NFκB T-cells ATM protein DNA E1A associated p300 protein Ets transcription factor immunoglobulin enhancer binding protein interstitial collagenase mitogenic agent protein p50 RNA selectin transcription factor transcription factor Rel transforming growth factor beta unclassified drug animal cell article cell cycle regulation cell interaction chromatin immunoprecipitation comparative study controlled study DNA repair embryo extracellular matrix gene gene expression gene identification gene location genetic analysis genome genomic instability human human cell introspection microarray analysis mouse nonhuman prediction promoter region protein analysis protein deficiency protein expression protein function protein interaction RNA interference SFN gene T lymphocyte technology tumor growth NFκB is an inducible transcription factor that controls kinetically complex patterns of gene expression. Several studies reveal multiple pathways linking NFκB to the promotion and progression of various cancers. Despite extensive interest and characterization, many NFκB controlled genes still remain to be identified. We used chromatin immunoprecipitation combined with microarray technology (ChIP/chip) to investigate the dynamic interaction of NFκB with the promoter regions of 100 genes known to be expressed in mitogen-induced T-cells. Six previously unrecognized NFκB controlled genes (ATM, EP300, TGFβ, Selectin, MMP-1 and SFN) were identified. Each gene is induced in mitogen-stimulated T-cells, repressed by pharmacological NFκB blockade, reduced in cells deficient in the p50 NFκB subunit and dramatically repressed by RNAi specifically designed against cRel. A coregulatory role for Ets transcription factors in the expression of the NFκB controlled genes was predicted by comparative promoter analysis and confirmed by ChIP and by functional disruption of Ets. NFκB deficiency produces a deficit in ATM function and DNA repair indicating an active role for NFκB in maintaining DNA integrity. These results define new potential targets and transcriptional networks governed by NFκB and provide novel functional insights for the role of NFκB in genomic stability, cell cycle control, cell-matrix and cell-cell interactions during tumor progressio. ©2009 Landes Bioscience. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15384101_v8_n13_p2093_DeSiervi |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
ATM ChIP/chip Ets NFκB T-cells ATM protein DNA E1A associated p300 protein Ets transcription factor immunoglobulin enhancer binding protein interstitial collagenase mitogenic agent protein p50 RNA selectin transcription factor transcription factor Rel transforming growth factor beta unclassified drug animal cell article cell cycle regulation cell interaction chromatin immunoprecipitation comparative study controlled study DNA repair embryo extracellular matrix gene gene expression gene identification gene location genetic analysis genome genomic instability human human cell introspection microarray analysis mouse nonhuman prediction promoter region protein analysis protein deficiency protein expression protein function protein interaction RNA interference SFN gene T lymphocyte technology tumor growth |
| spellingShingle |
ATM ChIP/chip Ets NFκB T-cells ATM protein DNA E1A associated p300 protein Ets transcription factor immunoglobulin enhancer binding protein interstitial collagenase mitogenic agent protein p50 RNA selectin transcription factor transcription factor Rel transforming growth factor beta unclassified drug animal cell article cell cycle regulation cell interaction chromatin immunoprecipitation comparative study controlled study DNA repair embryo extracellular matrix gene gene expression gene identification gene location genetic analysis genome genomic instability human human cell introspection microarray analysis mouse nonhuman prediction promoter region protein analysis protein deficiency protein expression protein function protein interaction RNA interference SFN gene T lymphocyte technology tumor growth De Siervi, A. De Luca, P. Moiola, C. Gueron, G. Tongbai, R. Chandramouli, G.V.R. Haggerty, C. Dzekunova, I. Petersen, D. Kawasaki, E. Whoon, J.K. Camphausen, K. Longo, D. Gardner, K. Identification of new Rel/NFκB regulatory networks by focused genome location analysis |
| topic_facet |
ATM ChIP/chip Ets NFκB T-cells ATM protein DNA E1A associated p300 protein Ets transcription factor immunoglobulin enhancer binding protein interstitial collagenase mitogenic agent protein p50 RNA selectin transcription factor transcription factor Rel transforming growth factor beta unclassified drug animal cell article cell cycle regulation cell interaction chromatin immunoprecipitation comparative study controlled study DNA repair embryo extracellular matrix gene gene expression gene identification gene location genetic analysis genome genomic instability human human cell introspection microarray analysis mouse nonhuman prediction promoter region protein analysis protein deficiency protein expression protein function protein interaction RNA interference SFN gene T lymphocyte technology tumor growth |
| description |
NFκB is an inducible transcription factor that controls kinetically complex patterns of gene expression. Several studies reveal multiple pathways linking NFκB to the promotion and progression of various cancers. Despite extensive interest and characterization, many NFκB controlled genes still remain to be identified. We used chromatin immunoprecipitation combined with microarray technology (ChIP/chip) to investigate the dynamic interaction of NFκB with the promoter regions of 100 genes known to be expressed in mitogen-induced T-cells. Six previously unrecognized NFκB controlled genes (ATM, EP300, TGFβ, Selectin, MMP-1 and SFN) were identified. Each gene is induced in mitogen-stimulated T-cells, repressed by pharmacological NFκB blockade, reduced in cells deficient in the p50 NFκB subunit and dramatically repressed by RNAi specifically designed against cRel. A coregulatory role for Ets transcription factors in the expression of the NFκB controlled genes was predicted by comparative promoter analysis and confirmed by ChIP and by functional disruption of Ets. NFκB deficiency produces a deficit in ATM function and DNA repair indicating an active role for NFκB in maintaining DNA integrity. These results define new potential targets and transcriptional networks governed by NFκB and provide novel functional insights for the role of NFκB in genomic stability, cell cycle control, cell-matrix and cell-cell interactions during tumor progressio. ©2009 Landes Bioscience. |
| format |
JOUR |
| author |
De Siervi, A. De Luca, P. Moiola, C. Gueron, G. Tongbai, R. Chandramouli, G.V.R. Haggerty, C. Dzekunova, I. Petersen, D. Kawasaki, E. Whoon, J.K. Camphausen, K. Longo, D. Gardner, K. |
| author_facet |
De Siervi, A. De Luca, P. Moiola, C. Gueron, G. Tongbai, R. Chandramouli, G.V.R. Haggerty, C. Dzekunova, I. Petersen, D. Kawasaki, E. Whoon, J.K. Camphausen, K. Longo, D. Gardner, K. |
| author_sort |
De Siervi, A. |
| title |
Identification of new Rel/NFκB regulatory networks by focused genome location analysis |
| title_short |
Identification of new Rel/NFκB regulatory networks by focused genome location analysis |
| title_full |
Identification of new Rel/NFκB regulatory networks by focused genome location analysis |
| title_fullStr |
Identification of new Rel/NFκB regulatory networks by focused genome location analysis |
| title_full_unstemmed |
Identification of new Rel/NFκB regulatory networks by focused genome location analysis |
| title_sort |
identification of new rel/nfκb regulatory networks by focused genome location analysis |
| url |
http://hdl.handle.net/20.500.12110/paper_15384101_v8_n13_p2093_DeSiervi |
| work_keys_str_mv |
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