IRF5:RelA interaction targets inflammatory genes in macrophages.
Interferon Regulatory Factor 5 (IRF5) plays a major role in setting up an inflammatory macrophage phenotype, but the molecular basis of its transcriptional activity is not fully understood. In this study, we conduct a comprehensive genome-wide analysis of IRF5 recruitment in macrophages stimulated w...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2014
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| _version_ | 1826258126501838848 |
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| author | Saliba, D Heger, A Eames, H Oikonomopoulos, S Teixeira, A Blazek, K Androulidaki, A Wong, D Goh, F Weiss, M Byrne, A Pasparakis, M Ragoussis, J Udalova, I |
| author_facet | Saliba, D Heger, A Eames, H Oikonomopoulos, S Teixeira, A Blazek, K Androulidaki, A Wong, D Goh, F Weiss, M Byrne, A Pasparakis, M Ragoussis, J Udalova, I |
| author_sort | Saliba, D |
| collection | OXFORD |
| description | Interferon Regulatory Factor 5 (IRF5) plays a major role in setting up an inflammatory macrophage phenotype, but the molecular basis of its transcriptional activity is not fully understood. In this study, we conduct a comprehensive genome-wide analysis of IRF5 recruitment in macrophages stimulated with bacterial lipopolysaccharide and discover that IRF5 binds to regulatory elements of highly transcribed genes. Analysis of protein:DNA microarrays demonstrates that IRF5 recognizes the canonical IRF-binding (interferon-stimulated response element [ISRE]) motif in vitro. However, IRF5 binding in vivo appears to rely on its interactions with other proteins. IRF5 binds to a noncanonical composite PU.1:ISRE motif, and its recruitment is aided by RelA. Global gene expression analysis in macrophages deficient in IRF5 and RelA highlights the direct role of the RelA:IRF5 cistrome in regulation of a subset of key inflammatory genes. We map the RelA:IRF5 interaction domain and suggest that interfering with it would offer selective targeting of macrophage inflammatory activities. |
| first_indexed | 2024-03-06T18:29:06Z |
| format | Journal article |
| id | oxford-uuid:090364ec-e993-4a83-b0a1-482aa66dd0f8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:29:06Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:090364ec-e993-4a83-b0a1-482aa66dd0f82022-03-26T09:15:59ZIRF5:RelA interaction targets inflammatory genes in macrophages.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:090364ec-e993-4a83-b0a1-482aa66dd0f8EnglishSymplectic Elements at Oxford2014Saliba, DHeger, AEames, HOikonomopoulos, STeixeira, ABlazek, KAndroulidaki, AWong, DGoh, FWeiss, MByrne, APasparakis, MRagoussis, JUdalova, IInterferon Regulatory Factor 5 (IRF5) plays a major role in setting up an inflammatory macrophage phenotype, but the molecular basis of its transcriptional activity is not fully understood. In this study, we conduct a comprehensive genome-wide analysis of IRF5 recruitment in macrophages stimulated with bacterial lipopolysaccharide and discover that IRF5 binds to regulatory elements of highly transcribed genes. Analysis of protein:DNA microarrays demonstrates that IRF5 recognizes the canonical IRF-binding (interferon-stimulated response element [ISRE]) motif in vitro. However, IRF5 binding in vivo appears to rely on its interactions with other proteins. IRF5 binds to a noncanonical composite PU.1:ISRE motif, and its recruitment is aided by RelA. Global gene expression analysis in macrophages deficient in IRF5 and RelA highlights the direct role of the RelA:IRF5 cistrome in regulation of a subset of key inflammatory genes. We map the RelA:IRF5 interaction domain and suggest that interfering with it would offer selective targeting of macrophage inflammatory activities. |
| spellingShingle | Saliba, D Heger, A Eames, H Oikonomopoulos, S Teixeira, A Blazek, K Androulidaki, A Wong, D Goh, F Weiss, M Byrne, A Pasparakis, M Ragoussis, J Udalova, I IRF5:RelA interaction targets inflammatory genes in macrophages. |
| title | IRF5:RelA interaction targets inflammatory genes in macrophages. |
| title_full | IRF5:RelA interaction targets inflammatory genes in macrophages. |
| title_fullStr | IRF5:RelA interaction targets inflammatory genes in macrophages. |
| title_full_unstemmed | IRF5:RelA interaction targets inflammatory genes in macrophages. |
| title_short | IRF5:RelA interaction targets inflammatory genes in macrophages. |
| title_sort | irf5 rela interaction targets inflammatory genes in macrophages |
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