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A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription
Cells maintain the balance between homeostasis and inflammation by adapting and integrating the activity of intracellular signaling cascades, including the JAK-STAT pathway. Our understanding of how a tailored switch from homeostasis to a strong receptor-dependent response is coordinated remains lim...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606597/ https://www.ncbi.nlm.nih.gov/pubmed/31266943 http://dx.doi.org/10.1038/s41467-019-10970-y |
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author | Platanitis, Ekaterini Demiroz, Duygu Schneller, Anja Fischer, Katrin Capelle, Christophe Hartl, Markus Gossenreiter, Thomas Müller, Mathias Novatchkova, Maria Decker, Thomas |
author_facet | Platanitis, Ekaterini Demiroz, Duygu Schneller, Anja Fischer, Katrin Capelle, Christophe Hartl, Markus Gossenreiter, Thomas Müller, Mathias Novatchkova, Maria Decker, Thomas |
author_sort | Platanitis, Ekaterini |
collection | PubMed |
description | Cells maintain the balance between homeostasis and inflammation by adapting and integrating the activity of intracellular signaling cascades, including the JAK-STAT pathway. Our understanding of how a tailored switch from homeostasis to a strong receptor-dependent response is coordinated remains limited. Here, we use an integrated transcriptomic and proteomic approach to analyze transcription-factor binding, gene expression and in vivo proximity-dependent labelling of proteins in living cells under homeostatic and interferon (IFN)-induced conditions. We show that interferons (IFN) switch murine macrophages from resting-state to induced gene expression by alternating subunits of transcription factor ISGF3. Whereas preformed STAT2-IRF9 complexes control basal expression of IFN-induced genes (ISG), both type I IFN and IFN-γ cause promoter binding of a complete ISGF3 complex containing STAT1, STAT2 and IRF9. In contrast to the dogmatic view of ISGF3 formation in the cytoplasm, our results suggest a model wherein the assembly of the ISGF3 complex occurs on DNA. |
format | Online Article Text |
id | pubmed-6606597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66065972019-07-05 A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription Platanitis, Ekaterini Demiroz, Duygu Schneller, Anja Fischer, Katrin Capelle, Christophe Hartl, Markus Gossenreiter, Thomas Müller, Mathias Novatchkova, Maria Decker, Thomas Nat Commun Article Cells maintain the balance between homeostasis and inflammation by adapting and integrating the activity of intracellular signaling cascades, including the JAK-STAT pathway. Our understanding of how a tailored switch from homeostasis to a strong receptor-dependent response is coordinated remains limited. Here, we use an integrated transcriptomic and proteomic approach to analyze transcription-factor binding, gene expression and in vivo proximity-dependent labelling of proteins in living cells under homeostatic and interferon (IFN)-induced conditions. We show that interferons (IFN) switch murine macrophages from resting-state to induced gene expression by alternating subunits of transcription factor ISGF3. Whereas preformed STAT2-IRF9 complexes control basal expression of IFN-induced genes (ISG), both type I IFN and IFN-γ cause promoter binding of a complete ISGF3 complex containing STAT1, STAT2 and IRF9. In contrast to the dogmatic view of ISGF3 formation in the cytoplasm, our results suggest a model wherein the assembly of the ISGF3 complex occurs on DNA. Nature Publishing Group UK 2019-07-02 /pmc/articles/PMC6606597/ /pubmed/31266943 http://dx.doi.org/10.1038/s41467-019-10970-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Platanitis, Ekaterini Demiroz, Duygu Schneller, Anja Fischer, Katrin Capelle, Christophe Hartl, Markus Gossenreiter, Thomas Müller, Mathias Novatchkova, Maria Decker, Thomas A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription |
title | A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription |
title_full | A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription |
title_fullStr | A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription |
title_full_unstemmed | A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription |
title_short | A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription |
title_sort | molecular switch from stat2-irf9 to isgf3 underlies interferon-induced gene transcription |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606597/ https://www.ncbi.nlm.nih.gov/pubmed/31266943 http://dx.doi.org/10.1038/s41467-019-10970-y |
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