Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells

Sherry TU, Kris HARDY, Chris SUTTON, Robert McCuaig, Jasmine Li, Jenny DUNN, Abel Tan, Vedran Brezar, Melanie Morris, Gareth Denyer, Sau Lee, Stephen J. Turner, Nabila Seddiki, Corey Smith, Rajiv Khanna, Sudha RAO

Research output: Contribution to journalArticle

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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, NF-κ B, 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.

Original languageEnglish
Article number44825
Pages (from-to)1-20
Number of pages20
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 20 Mar 2017

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Chromatin
T-Lymphocytes
Nucleic Acid Regulatory Sequences
Acetylation
Histones
Genes
Transcription Factors
Maintenance
Infection

Cite this

TU, S., HARDY, K., SUTTON, C., McCuaig, R., Li, J., DUNN, J., ... RAO, S. (2017). Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells. Scientific Reports, 7, 1-20. [44825]. https://doi.org/10.1038/srep44825
TU, Sherry ; HARDY, Kris ; SUTTON, Chris ; McCuaig, Robert ; Li, Jasmine ; DUNN, Jenny ; Tan, Abel ; Brezar, Vedran ; Morris, Melanie ; Denyer, Gareth ; Lee, Sau ; Turner, Stephen J. ; Seddiki, Nabila ; Smith, Corey ; Khanna, Rajiv ; RAO, Sudha. / Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells. In: Scientific Reports. 2017 ; Vol. 7. pp. 1-20.
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title = "Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells",
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, NF-κ B, 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.",
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author = "Sherry TU and Kris HARDY and Chris SUTTON and Robert McCuaig and Jasmine Li and Jenny DUNN and Abel Tan and Vedran Brezar and Melanie Morris and Gareth Denyer and Sau Lee and Turner, {Stephen J.} and Nabila Seddiki and Corey Smith and Rajiv Khanna and Sudha RAO",
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TU, S, HARDY, K, SUTTON, C, McCuaig, R, Li, J, DUNN, J, Tan, A, Brezar, V, Morris, M, Denyer, G, Lee, S, Turner, SJ, Seddiki, N, Smith, C, Khanna, R & RAO, S 2017, 'Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells', Scientific Reports, vol. 7, 44825, pp. 1-20. https://doi.org/10.1038/srep44825

Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells. / TU, Sherry; HARDY, Kris; SUTTON, Chris; McCuaig, Robert; Li, Jasmine; DUNN, Jenny; Tan, Abel; Brezar, Vedran; Morris, Melanie; Denyer, Gareth; Lee, Sau; Turner, Stephen J.; Seddiki, Nabila; Smith, Corey; Khanna, Rajiv; RAO, Sudha.

In: Scientific Reports, Vol. 7, 44825, 20.03.2017, p. 1-20.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells

AU - TU, Sherry

AU - HARDY, Kris

AU - SUTTON, Chris

AU - McCuaig, Robert

AU - Li, Jasmine

AU - DUNN, Jenny

AU - Tan, Abel

AU - Brezar, Vedran

AU - Morris, Melanie

AU - Denyer, Gareth

AU - Lee, Sau

AU - Turner, Stephen J.

AU - Seddiki, Nabila

AU - Smith, Corey

AU - Khanna, Rajiv

AU - RAO, Sudha

PY - 2017/3/20

Y1 - 2017/3/20

N2 - 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, NF-κ B, 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.

AB - 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, NF-κ B, 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.

KW - Acetylation

KW - Binding Sites

KW - CD4-Positive T-Lymphocytes/immunology

KW - Chromatin/genetics

KW - Chromatin Assembly and Disassembly

KW - GATA Transcription Factors/metabolism

KW - Gene Expression Profiling

KW - Histones/metabolism

KW - Humans

KW - Immunologic Memory/genetics

KW - Lymphocyte Activation/genetics

KW - NFATC Transcription Factors/metabolism

KW - Promoter Regions, Genetic

KW - Protein Binding

KW - T-Lymphocytes/immunology

KW - Transcription, Genetic

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UR - http://www.mendeley.com/research/priming-transcriptional-memory-responses-via-chromatin-accessibility-landscape-t-cells

U2 - 10.1038/srep44825

DO - 10.1038/srep44825

M3 - Article

VL - 7

SP - 1

EP - 20

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 44825

ER -