Universität zu Köln

Saliba, David G., Heger, Andreas ORCID: 0000-0001-7720-0447, Eames, Hayley L., Oikonomopoulos, Spyros, Teixeira, Ana, Blazek, Katrina ORCID: 0000-0002-4439-4756, Androulidaki, Ariadne, Wong, Daniel, Goh, Fui G., Weiss, Miriam, Byrne, Adam ORCID: 0000-0001-8352-3007, Pasparakis, Manolis ORCID: 0000-0002-9870-0966, Ragoussis, Jiannis and Udalova, Irina A. (2014). IRF5:RelA Interaction Targets Inflammatory Genes in Macrophages. Cell Reports, 8 (5). S. 1308 - 1318. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Saliba, David G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heger, Andreas UNSPECIFIED orcid.org/0000-0001-7720-0447 UNSPECIFIED Eames, Hayley L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Oikonomopoulos, Spyros UNSPECIFIED UNSPECIFIED UNSPECIFIED Teixeira, Ana UNSPECIFIED UNSPECIFIED UNSPECIFIED Blazek, Katrina UNSPECIFIED orcid.org/0000-0002-4439-4756 UNSPECIFIED Androulidaki, Ariadne UNSPECIFIED UNSPECIFIED UNSPECIFIED Wong, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Goh, Fui G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weiss, Miriam UNSPECIFIED UNSPECIFIED UNSPECIFIED Byrne, Adam UNSPECIFIED orcid.org/0000-0001-8352-3007 UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED Ragoussis, Jiannis UNSPECIFIED UNSPECIFIED UNSPECIFIED Udalova, Irina A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-428775
DOI:	10.1016/j.celrep.2014.07.034
Journal or Publication Title:	Cell Reports
Volume:	8
Number:	5
Page Range:	S. 1308 - 1318
Date:	2014
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRANSCRIPTION FACTORS; IDENTIFICATION; EXPRESSION; DIVERSITY; PROGRAM; RISK; IRF Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/42877