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Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells
Memory T cells exhibit transcriptional memory and “remember” their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357947/ https://www.ncbi.nlm.nih.gov/pubmed/28317936 http://dx.doi.org/10.1038/srep44825 |
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author | Tu, Wen Juan Hardy, Kristine Sutton, Christopher R. McCuaig, Robert Li, Jasmine Dunn, Jenny Tan, Abel Brezar, Vedran Morris, Melanie Denyer, Gareth Lee, Sau Kuen Turner, Stephen J. Seddiki, Nabila Smith, Corey Khanna, Rajiv Rao, Sudha |
author_facet | Tu, Wen Juan Hardy, Kristine Sutton, Christopher R. McCuaig, Robert Li, Jasmine Dunn, Jenny Tan, Abel Brezar, Vedran Morris, Melanie Denyer, Gareth Lee, Sau Kuen Turner, Stephen J. Seddiki, Nabila Smith, Corey Khanna, Rajiv Rao, Sudha |
author_sort | Tu, Wen Juan |
collection | PubMed |
description | Memory T cells exhibit transcriptional memory and “remember” their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes. Increased accessibility occurred largely in distal regulatory regions and was associated with increased histone acetylation and relative H3.3 deposition. The enhanced re-stimulation response was linked to the strength of initial PKC-induced signalling, and PKC-sensitive increases in accessibility upon initial stimulation showed higher accessibility on re-stimulation. While accessibility maintenance was associated with ETS-1, accessibility at re-stimulation-specific regions was linked to NFAT, especially in combination with ETS-1, EGR, GATA, NFκB, and NR4A. Furthermore, NFATC1 was directly regulated by ETS-1 at an enhancer region. In contrast to the factors that increased accessibility, signalling from bHLH and ZEB family members enhanced decreased accessibility upon re-stimulation. Interplay between distal regulatory elements, accessibility, and the combined action of sequence-specific transcription factors allows transcriptional memory-responsive genes to “remember” their initial environmental encounter. |
format | Online Article Text |
id | pubmed-5357947 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53579472017-03-22 Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells Tu, Wen Juan Hardy, Kristine Sutton, Christopher R. McCuaig, Robert Li, Jasmine Dunn, Jenny Tan, Abel Brezar, Vedran Morris, Melanie Denyer, Gareth Lee, Sau Kuen Turner, Stephen J. Seddiki, Nabila Smith, Corey Khanna, Rajiv Rao, Sudha Sci Rep Article Memory T cells exhibit transcriptional memory and “remember” their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes. Increased accessibility occurred largely in distal regulatory regions and was associated with increased histone acetylation and relative H3.3 deposition. The enhanced re-stimulation response was linked to the strength of initial PKC-induced signalling, and PKC-sensitive increases in accessibility upon initial stimulation showed higher accessibility on re-stimulation. While accessibility maintenance was associated with ETS-1, accessibility at re-stimulation-specific regions was linked to NFAT, especially in combination with ETS-1, EGR, GATA, NFκB, and NR4A. Furthermore, NFATC1 was directly regulated by ETS-1 at an enhancer region. In contrast to the factors that increased accessibility, signalling from bHLH and ZEB family members enhanced decreased accessibility upon re-stimulation. Interplay between distal regulatory elements, accessibility, and the combined action of sequence-specific transcription factors allows transcriptional memory-responsive genes to “remember” their initial environmental encounter. Nature Publishing Group 2017-03-20 /pmc/articles/PMC5357947/ /pubmed/28317936 http://dx.doi.org/10.1038/srep44825 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Tu, Wen Juan Hardy, Kristine Sutton, Christopher R. McCuaig, Robert Li, Jasmine Dunn, Jenny Tan, Abel Brezar, Vedran Morris, Melanie Denyer, Gareth Lee, Sau Kuen Turner, Stephen J. Seddiki, Nabila Smith, Corey Khanna, Rajiv Rao, Sudha Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells |
title | Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells |
title_full | Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells |
title_fullStr | Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells |
title_full_unstemmed | Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells |
title_short | Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells |
title_sort | priming of transcriptional memory responses via the chromatin accessibility landscape in t cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357947/ https://www.ncbi.nlm.nih.gov/pubmed/28317936 http://dx.doi.org/10.1038/srep44825 |
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