IRF5:RelA interaction targets inflammatory genes in macrophages.
作者： David G. Saliba , Andreas Heger , Hayley L. Eames , Spyros Oikonomopoulos , Ana Teixeira
DOI: 10.1016/J.CELREP.2014.07.034
关键词:
摘要: 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 comprehensive genome-wide analysis IRF5 recruitment macrophages stimulated with bacterial lipopolysaccharide and discover that binds to regulatory elements highly transcribed genes. Analysis protein:DNA microarrays demonstrates recognizes canonical IRF-binding (interferon-stimulated response element [ISRE]) motif in vitro. However, binding in vivo appears rely on interactions other proteins. noncanonical composite PU.1:ISRE motif, aided by RelA. Global gene expression deficient RelA highlights direct RelA:IRF5 cistrome regulation subset key We map interaction domain suggest interfering it would offer selective targeting activities.
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Gioacchino Natoli, NF-κB and chromatin: ten years on the path from basic mechanisms to candidate drugs Immunological Reviews. ,vol. 246, pp. 183- 192 ,(2012) , 10.1111/J.1600-065X.2012.01103.X
Andrew J. Fleetwood, Toby Lawrence, John A. Hamilton, Andrew D. Cook, Granulocyte-Macrophage Colony-Stimulating Factor (CSF) and Macrophage CSF-Dependent Macrophage Phenotypes Display Differences in Cytokine Profiles and Transcription Factor Activities: Implications for CSF Blockade in Inflammation Journal of Immunology. ,vol. 178, pp. 5245- 5252 ,(2007) , 10.4049/JIMMUNOL.178.8.5245
Thomas Krausgruber, Katrina Blazek, Tim Smallie, Saba Alzabin, Helen Lockstone, Natasha Sahgal, Tracy Hussell, Marc Feldmann, Irina A Udalova, IRF5 Promotes Inflammatory Macrophage Polarization and TH1-TH17 Responses Nature Immunology. ,vol. 12, pp. 231- 238 ,(2011) , 10.1038/NI.1990
Thomas Krausgruber, David Saliba, Grigory Ryzhakov, Alessandra Lanfrancotti, Katrina Blazek, Irina A. Udalova, IRF5 is required for late-phase TNF secretion by human dendritic cells Blood. ,vol. 115, pp. 4421- 4430 ,(2010) , 10.1182/BLOOD-2010-01-263020
Trevor Siggers, Abraham B Chang, Ana Teixeira, Daniel Wong, Kevin J Williams, Bilal Ahmed, Jiannis Ragoussis, Irina A Udalova, Stephen T Smale, Martha L Bulyk, Principles of dimer-specific gene regulation revealed by a comprehensive characterization of NF-κB family DNA binding Nature Immunology. ,vol. 13, pp. 95- 102 ,(2012) , 10.1038/NI.2151
Ching-Aeng Lim, Fei Yao, Joyce Jing-Yi Wong, Joshy George, Han Xu, Kuo Ping Chiu, Wing-Kin Sung, Leonard Lipovich, Vinsensius B Vega, Joanne Chen, Atif Shahab, Xiao Dong Zhao, Martin Hibberd, Chia-Lin Wei, Bing Lim, Huck-Hui Ng, Yijun Ruan, Keh-Chuang Chin, None, Genome-wide Mapping of RELA(p65) Binding Identifies E2F1 as a Transcriptional Activator Recruited by NF-κB upon TLR4 Activation Molecular Cell. ,vol. 27, pp. 622- 635 ,(2007) , 10.1016/J.MOLCEL.2007.06.038
H.L. Eames, D.G. Saliba, T. Krausgruber, A. Lanfrancotti, G. Ryzhakov, I.A. Udalova, KAP1/TRIM28: an inhibitor of IRF5 function in inflammatory macrophages. Immunobiology. ,vol. 217, pp. 1315- 1324 ,(2012) , 10.1016/J.IMBIO.2012.07.026
Francesca De Santa, Maria Grazia Totaro, Elena Prosperini, Samuele Notarbartolo, Giuseppe Testa, Gioacchino Natoli, The Histone H3 Lysine-27 Demethylase Jmjd3 Links Inflammation to Inhibition of Polycomb-Mediated Gene Silencing Cell. ,vol. 130, pp. 1083- 1094 ,(2007) , 10.1016/J.CELL.2007.08.019
Tomohiko Tamura, Pratima Thotakura, Tetsuya S. Tanaka, Minoru S. H. Ko, Keiko Ozato, Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages Blood. ,vol. 106, pp. 1938- 1947 ,(2005) , 10.1182/BLOOD-2005-01-0080
A L Brass, E Kehrli, C F Eisenbeis, U Storb, H Singh, Pip, a lymphoid-restricted IRF, contains a regulatory domain that is important for autoinhibition and ternary complex formation with the Ets factor PU.1. Genes & Development. ,vol. 10, pp. 2335- 2347 ,(1996) , 10.1101/GAD.10.18.2335