Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells
Identifieur interne : 000554 ( Main/Exploration ); précédent : 000553; suivant : 000555Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells
Auteurs : Wen Juan Tu [Australie] ; Kristine Hardy [Australie] ; Christopher R. Sutton [Australie] ; Robert Mccuaig [Australie] ; Jasmine Li [Australie] ; Jenny Dunn [Australie] ; Abel Tan [Australie] ; Vedran Brezar [France] ; Melanie Morris [Australie] ; Gareth Denyer [Australie] ; Sau Kuen Lee [Australie] ; Stephen J. Turner [Australie] ; Nabila Seddiki [France] ; Corey Smith [Australie] ; Rajiv Khanna [Australie] ; Sudha Rao [Australie]Source :
- Scientific Reports [ 2045-2322 ] ; 2017.
Abstract
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,
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DOI: 10.1038/srep44825
PubMed: 28317936
PubMed Central: 5357947
Affiliations:
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Sutton</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Faculty of Education, Science, Technology & Mathematics, University of Canberra</institution>, Canberra, Australian Capital Territory 2617,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mccuaig, Robert" sort="Mccuaig, Robert" uniqKey="Mccuaig R" first="Robert" last="Mccuaig">Robert Mccuaig</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Faculty of Education, Science, Technology & Mathematics, University of Canberra</institution>, Canberra, Australian Capital Territory 2617,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Jasmine" sort="Li, Jasmine" uniqKey="Li J" first="Jasmine" last="Li">Jasmine 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see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Khanna, Rajiv" sort="Khanna, Rajiv" uniqKey="Khanna R" first="Rajiv" last="Khanna">Rajiv Khanna</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>QIMR Berghofer Centre for Immunotherapy and Vaccine Development QIMR Berghofer Medical Research Institute</institution>, Brisbane, Queensland,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute</institution>, Brisbane, Queensland,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rao, Sudha" sort="Rao, Sudha" uniqKey="Rao S" first="Sudha" 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type="main">Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells</title><author><name sortKey="Tu, Wen Juan" sort="Tu, Wen Juan" uniqKey="Tu W" first="Wen Juan" last="Tu">Wen Juan Tu</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Faculty of Education, Science, Technology & Mathematics, University of Canberra</institution>, Canberra, Australian Capital Territory 2617,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hardy, Kristine" sort="Hardy, Kristine" uniqKey="Hardy K" first="Kristine" last="Hardy">Kristine Hardy</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Faculty of Education, Science, Technology & Mathematics, University of Canberra</institution>, Canberra, Australian Capital Territory 2617,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sutton, Christopher R" sort="Sutton, Christopher R" uniqKey="Sutton C" first="Christopher R." last="Sutton">Christopher R. Sutton</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Faculty of Education, Science, Technology & Mathematics, University of Canberra</institution>, Canberra, Australian Capital Territory 2617,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mccuaig, Robert" sort="Mccuaig, Robert" uniqKey="Mccuaig R" first="Robert" last="Mccuaig">Robert Mccuaig</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Faculty of Education, Science, Technology & Mathematics, University of Canberra</institution>, Canberra, Australian Capital Territory 2617,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Jasmine" sort="Li, Jasmine" uniqKey="Li J" first="Jasmine" last="Li">Jasmine Li</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Microbiology, Biomedical Discovery Institute, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Microbiology & Immunology, The Doherty Institute for Infection and Immunity, University of Melbourne</institution>, Victoria 3010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dunn, Jenny" sort="Dunn, Jenny" uniqKey="Dunn J" first="Jenny" last="Dunn">Jenny Dunn</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Faculty of Education, Science, Technology & Mathematics, University of Canberra</institution>, Canberra, Australian Capital Territory 2617,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tan, Abel" sort="Tan, Abel" uniqKey="Tan A" first="Abel" last="Tan">Abel Tan</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Faculty of Education, Science, Technology & Mathematics, University of Canberra</institution>, Canberra, Australian Capital Territory 2617,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Brezar, Vedran" sort="Brezar, Vedran" uniqKey="Brezar V" first="Vedran" last="Brezar">Vedran Brezar</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>INSERM U955 Eq16 Faculte de medicine Henri Mondor and Universite Paris-Est, Creteil/Vaccine Research Institute</institution>, Creteil 94010,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Morris, Melanie" sort="Morris, Melanie" uniqKey="Morris M" first="Melanie" last="Morris">Melanie Morris</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Faculty of Education, Science, Technology & Mathematics, University of Canberra</institution>, Canberra, Australian Capital Territory 2617,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Denyer, Gareth" sort="Denyer, Gareth" uniqKey="Denyer G" first="Gareth" last="Denyer">Gareth Denyer</name><affiliation wicri:level="1"><nlm:aff id="a5"><institution>School of Molecular Bioscience, The University of Sydney</institution>, Sydney, NSW,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lee, Sau Kuen" sort="Lee, Sau Kuen" uniqKey="Lee S" first="Sau Kuen" last="Lee">Sau Kuen Lee</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>QIMR Berghofer Centre for Immunotherapy and Vaccine Development QIMR Berghofer Medical Research Institute</institution>, Brisbane, Queensland,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute</institution>, Brisbane, Queensland,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Turner, Stephen J" sort="Turner, Stephen J" uniqKey="Turner S" first="Stephen J." last="Turner">Stephen J. Turner</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Microbiology, Biomedical Discovery Institute, Monash University</institution>, Clayton, Victoria 3800,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Department of Microbiology & Immunology, The Doherty Institute for Infection and Immunity, University of Melbourne</institution>, Victoria 3010,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Seddiki, Nabila" sort="Seddiki, Nabila" uniqKey="Seddiki N" first="Nabila" last="Seddiki">Nabila Seddiki</name><affiliation wicri:level="1"><nlm:aff id="a4"><institution>INSERM U955 Eq16 Faculte de medicine Henri Mondor and Universite Paris-Est, Creteil/Vaccine Research Institute</institution>, Creteil 94010,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Smith, Corey" sort="Smith, Corey" uniqKey="Smith C" first="Corey" last="Smith">Corey Smith</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>QIMR Berghofer Centre for Immunotherapy and Vaccine Development QIMR Berghofer Medical Research Institute</institution>, Brisbane, Queensland,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute</institution>, Brisbane, Queensland,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Khanna, Rajiv" sort="Khanna, Rajiv" uniqKey="Khanna R" first="Rajiv" last="Khanna">Rajiv Khanna</name><affiliation wicri:level="1"><nlm:aff id="a6"><institution>QIMR Berghofer Centre for Immunotherapy and Vaccine Development QIMR Berghofer Medical Research Institute</institution>, Brisbane, Queensland,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a7"><institution>Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute</institution>, Brisbane, Queensland,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rao, Sudha" sort="Rao, Sudha" uniqKey="Rao S" first="Sudha" last="Rao">Sudha Rao</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Faculty of Education, Science, Technology & Mathematics, University of Canberra</institution>, Canberra, Australian Capital Territory 2617,<country>Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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, <italic>NFATC1</italic> 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Weng, N P" uniqKey="Weng N">N. P. Weng</name></author><author><name sortKey="Araki, Y" uniqKey="Araki Y">Y. Araki</name></author><author><name sortKey="Subedi, K" uniqKey="Subedi K">K. Subedi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, K" uniqKey="Liu K">K. 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Sutton</name><name sortKey="Tan, Abel" sort="Tan, Abel" uniqKey="Tan A" first="Abel" last="Tan">Abel Tan</name><name sortKey="Turner, Stephen J" sort="Turner, Stephen J" uniqKey="Turner S" first="Stephen J." last="Turner">Stephen J. Turner</name><name sortKey="Turner, Stephen J" sort="Turner, Stephen J" uniqKey="Turner S" first="Stephen J." last="Turner">Stephen J. Turner</name></country><country name="France"><noRegion><name sortKey="Brezar, Vedran" sort="Brezar, Vedran" uniqKey="Brezar V" first="Vedran" last="Brezar">Vedran Brezar</name></noRegion><name sortKey="Seddiki, Nabila" sort="Seddiki, Nabila" uniqKey="Seddiki N" first="Nabila" last="Seddiki">Nabila Seddiki</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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