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AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation
Activation of T cells is dependent on the organized and timely opening and closing of chromatin. Herein, we identify AP-1 as the transcription factor that directs most of this remodeling. Chromatin accessibility profiling showed quick opening of closed chromatin in naive T cells within 5 h of activa...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037242/ https://www.ncbi.nlm.nih.gov/pubmed/31653690 http://dx.doi.org/10.1084/jem.20182009 |
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author | Yukawa, Masashi Jagannathan, Sajjeev Vallabh, Sushmitha Kartashov, Andrey V. Chen, Xiaoting Weirauch, Matthew T. Barski, Artem |
author_facet | Yukawa, Masashi Jagannathan, Sajjeev Vallabh, Sushmitha Kartashov, Andrey V. Chen, Xiaoting Weirauch, Matthew T. Barski, Artem |
author_sort | Yukawa, Masashi |
collection | PubMed |
description | Activation of T cells is dependent on the organized and timely opening and closing of chromatin. Herein, we identify AP-1 as the transcription factor that directs most of this remodeling. Chromatin accessibility profiling showed quick opening of closed chromatin in naive T cells within 5 h of activation. These newly opened regions were strongly enriched for the AP-1 motif, and indeed, ChIP-seq demonstrated AP-1 binding at >70% of them. Broad inhibition of AP-1 activity prevented chromatin opening at AP-1 sites and reduced the expression of nearby genes. Similarly, induction of anergy in the absence of co-stimulation during activation was associated with reduced induction of AP-1 and a failure of proper chromatin remodeling. The translational relevance of these findings was highlighted by the substantial overlap of AP-1–dependent elements with risk loci for multiple immune diseases, including multiple sclerosis, inflammatory bowel disease, and allergic disease. Our findings define AP-1 as the key link between T cell activation and chromatin remodeling. |
format | Online Article Text |
id | pubmed-7037242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-70372422020-07-06 AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation Yukawa, Masashi Jagannathan, Sajjeev Vallabh, Sushmitha Kartashov, Andrey V. Chen, Xiaoting Weirauch, Matthew T. Barski, Artem J Exp Med Research Articles Activation of T cells is dependent on the organized and timely opening and closing of chromatin. Herein, we identify AP-1 as the transcription factor that directs most of this remodeling. Chromatin accessibility profiling showed quick opening of closed chromatin in naive T cells within 5 h of activation. These newly opened regions were strongly enriched for the AP-1 motif, and indeed, ChIP-seq demonstrated AP-1 binding at >70% of them. Broad inhibition of AP-1 activity prevented chromatin opening at AP-1 sites and reduced the expression of nearby genes. Similarly, induction of anergy in the absence of co-stimulation during activation was associated with reduced induction of AP-1 and a failure of proper chromatin remodeling. The translational relevance of these findings was highlighted by the substantial overlap of AP-1–dependent elements with risk loci for multiple immune diseases, including multiple sclerosis, inflammatory bowel disease, and allergic disease. Our findings define AP-1 as the key link between T cell activation and chromatin remodeling. Rockefeller University Press 2019-10-25 /pmc/articles/PMC7037242/ /pubmed/31653690 http://dx.doi.org/10.1084/jem.20182009 Text en © 2019 Yukawa et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Yukawa, Masashi Jagannathan, Sajjeev Vallabh, Sushmitha Kartashov, Andrey V. Chen, Xiaoting Weirauch, Matthew T. Barski, Artem AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation |
title | AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation |
title_full | AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation |
title_fullStr | AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation |
title_full_unstemmed | AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation |
title_short | AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation |
title_sort | ap-1 activity induced by co-stimulation is required for chromatin opening during t cell activation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037242/ https://www.ncbi.nlm.nih.gov/pubmed/31653690 http://dx.doi.org/10.1084/jem.20182009 |
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