Nicolas Matt, PhD. Group leader at UPR 9022 – M3i CNRS
Contact
Nicolas Matt
Phone
E-Mail
Website
UPR 9022 – M3I CNRS
Institut de Biologie Moléculaire et Cellulaire du CNRS
2 allée Konrad Roentgen
67084 Strasbourg Cedex
France
Research topics
- Transcriptional network induced upon pathogen specific infection
- RNA-Protein interaction, translational control and regulation of transcription
Role in NetRNA
The aim of our research is to decipher the complex regulatory network underlying the innate immune response. Through the understanding of specific RNA-protein interaction during transcription and translation of NF-kB induced target genes, we expect to understand the molecular basis of selectivity in the innate immune response both in Drosophila and in mammals.
Working Group
Publications
2014
Bonnay, F; Nguyen, X H; Cohen-Berros, E; Troxler, L; Batsche, E; Camonis, J; Takeuchi, O; Reichhart, J M; Matt, N
Akirin specifies NF-kappaB selectivity of Drosophila innate immune response via chromatin remodeling Article de journal
Dans: Embo J, vol. 33, no. 20, p. 2349-62, 2014, ISBN: 25180232, (1460-2075 (Electronic) 0261-4189 (Linking) Journal Article Research Support, Non-U.S. Gov't).
@article{nokey,
title = {Akirin specifies NF-kappaB selectivity of Drosophila innate immune response via chromatin remodeling},
author = {F Bonnay and X H Nguyen and E Cohen-Berros and L Troxler and E Batsche and J Camonis and O Takeuchi and J M Reichhart and N Matt},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=25180232},
doi = {10.15252/embj.201488456},
isbn = {25180232},
year = {2014},
date = {2014-01-01},
journal = {Embo J},
volume = {33},
number = {20},
pages = {2349-62},
abstract = {The network of NF-kappaB-dependent transcription that activates both pro- and anti-inflammatory genes in mammals is still unclear. As NF-kappaB factors are evolutionarily conserved, we used Drosophila to understand this network. The NF-kappaB transcription factor Relish activates effector gene expression following Gram-negative bacterial immune challenge. Here, we show, using a genome-wide approach, that the conserved nuclear protein Akirin is a NF-kappaB co-factor required for the activation of a subset of Relish-dependent genes correlating with the presence of H3K4ac epigenetic marks. A large-scale unbiased proteomic analysis revealed that Akirin orchestrates NF-kappaB transcriptional selectivity through the recruitment of the Osa-containing-SWI/SNF-like Brahma complex (BAP). Immune challenge in Drosophila shows that Akirin is required for the transcription of a subset of effector genes, but dispensable for the transcription of genes that are negative regulators of the innate immune response. Therefore, Akirins act as molecular selectors specifying the choice between subsets of NF-kappaB target genes. The discovery of this mechanism, conserved in mammals, paves the way for the establishment of more specific and less toxic anti-inflammatory drugs targeting pro-inflammatory genes.},
note = {1460-2075 (Electronic)
0261-4189 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2013
Bonnay, F; Cohen-Berros, E; Hoffmann, M; Kim, S Y; Boulianne, G L; Hoffmann, J A; Matt, N; Reichhart, J M
Big bang gene modulates gut immune tolerance in Drosophila Article de journal
Dans: Proc Natl Acad Sci U S A, vol. 110, no. 8, p. 2957-62, 2013, ISBN: 23378635, (1091-6490 (Electronic) 0027-8424 (Linking) Journal Article Research Support, Non-U.S. Gov't).
@article{nokey,
title = {Big bang gene modulates gut immune tolerance in Drosophila},
author = {F Bonnay and E Cohen-Berros and M Hoffmann and S Y Kim and G L Boulianne and J A Hoffmann and N Matt and J M Reichhart},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=23378635},
doi = {10.1073/pnas.1221910110},
isbn = {23378635},
year = {2013},
date = {2013-01-01},
journal = {Proc Natl Acad Sci U S A},
volume = {110},
number = {8},
pages = {2957-62},
abstract = {Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.},
note = {1091-6490 (Electronic)
0027-8424 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2012
Zuniga, A; Laurent, F; Lopez-Rios, J; Klasen, C; Matt, N; Zeller, R
Conserved cis-regulatory regions in a large genomic landscape control SHH and BMP-regulated Gremlin1 expression in mouse limb buds Article de journal
Dans: BMC Dev Biol, vol. 12, p. 23, 2012, ISBN: 22888807, (1471-213X (Electronic) 1471-213X (Linking) Journal Article Research Support, Non-U.S. Gov't).
@article{nokey,
title = {Conserved cis-regulatory regions in a large genomic landscape control SHH and BMP-regulated Gremlin1 expression in mouse limb buds},
author = {A Zuniga and F Laurent and J Lopez-Rios and C Klasen and N Matt and R Zeller},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22888807},
doi = {10.1186/1471-213X-12-23},
isbn = {22888807},
year = {2012},
date = {2012-01-01},
journal = {BMC Dev Biol},
volume = {12},
pages = {23},
abstract = {BACKGROUND: Mouse limb bud is a prime model to study the regulatory interactions that control vertebrate organogenesis. Major aspects of limb bud development are controlled by feedback loops that define a self-regulatory signalling system. The SHH/GREM1/AER-FGF feedback loop forms the core of this signalling system that operates between the posterior mesenchymal organiser and the ectodermal signalling centre. The BMP antagonist Gremlin1 (GREM1) is a critical node in this system, whose dynamic expression is controlled by BMP, SHH, and FGF signalling and key to normal progression of limb bud development. Previous analysis identified a distant cis-regulatory landscape within the neighbouring Formin1 (Fmn1) locus that is required for Grem1 expression, reminiscent of the genomic landscapes controlling HoxD and Shh expression in limb buds. RESULTS: Three highly conserved regions (HMCO1-3) were identified within the previously defined critical genomic region and tested for their ability to regulate Grem1 expression in mouse limb buds. Using a combination of BAC and conventional transgenic approaches, a 9 kb region located ~70 kb downstream of the Grem1 transcription unit was identified. This region, termed Grem1 Regulatory Sequence 1 (GRS1), is able to recapitulate major aspects of Grem1 expression, as it drives expression of a LacZ reporter into the posterior and, to a lesser extent, in the distal-anterior mesenchyme. Crossing the GRS1 transgene into embryos with alterations in the SHH and BMP pathways established that GRS1 depends on SHH and is modulated by BMP signalling, i.e. integrates inputs from these pathways. Chromatin immunoprecipitation revealed interaction of endogenous GLI3 proteins with the core cis-regulatory elements in the GRS1 region. As GLI3 is a mediator of SHH signal transduction, these results indicated that SHH directly controls Grem1 expression through the GRS1 region. Finally, all cis-regulatory regions within the Grem1 genomic landscape locate to the DNAse I hypersensitive sites identified in this genomic region by the ENCODE consortium. CONCLUSIONS: This study establishes that distant cis-regulatory regions scattered through a larger genomic landscape control the highly dynamic expression of Grem1, which is key to normal progression of mouse limb bud development.},
note = {1471-213X (Electronic)
1471-213X (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2011
Aoun, R Bou; Hetru, C; Troxler, L; Doucet, D; Ferrandon, D; Matt, N
Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster Article de journal
Dans: J Innate Immun, vol. 3, no. 1, p. 52-64, 2011, ISBN: 21063077, (1662-8128 (Electronic) 1662-811X (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't).
@article{nokey,
title = {Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster},
author = {R Bou Aoun and C Hetru and L Troxler and D Doucet and D Ferrandon and N Matt},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21063077},
doi = {10.1159/000321554},
isbn = {21063077},
year = {2011},
date = {2011-01-01},
journal = {J Innate Immun},
volume = {3},
number = {1},
pages = {52-64},
abstract = {Thioester-containing proteins (TEPs) are conserved proteins among insects that are thought to be involved in innate immunity. In Drosophila, the Tep family is composed of 6 genes named Tep1-Tep6. In this study, we investigated the phylogeny, expression pattern and roles of these genes in the host defense of Drosophila. Protostomian Tep genes are clustered in 3 distinct branches, 1 of which is specific to mosquitoes. Most D. melanogaster Tep genes are expressed in hemocytes, can be induced in the fat body, and are expressed in specific regions of the hypodermis. This expression pattern is consistent with a role in innate immunity. However, we find that TEP1, TEP2, and TEP4 are not strictly required in the body cavity to fight several bacterial and fungal infections. One possibility is that Drosophila TEPs act redundantly or that their absence can be compensated by other components of the immune response. TEPs may thus provide a subtle selective advantage during evolution. Alternatively, they may be required in host defense against specific as yet unidentified natural pathogens of Drosophila.},
note = {1662-8128 (Electronic)
1662-811X (Linking)
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't},
keywords = {},
pubstate = {published},
tppubtype = {article}
}