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

Wen Juan Tu; Kristine Hardy; Christopher R. Sutton; Robert McCuaig; Jasmine Li; Jenny Dunn; Abel Tan; Vedran Brezar; Melanie Morris; Gareth Denyer; Sau Kuen Lee; Stephen J. Turner; Nabila Seddiki; Corey Smith; Rajiv Khanna; Sudha Rao

doi:10.1038/srep44825

journal article Open Access Mar 20, 2017

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

Wen Juan Tu Kristine Hardy Christopher R. Sutton Robert McCuaig Jasmine Li Jenny Dunn Abel Tan Vedran Brezar Melanie Morris Gareth Denyer Sau Kuen Lee Stephen J. Turner

Nabila Seddiki Corey Smith

Rajiv Khanna

Sudha Rao

Scientific Reports Vol. 7 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/srep44825

Abstract

AbstractMemory 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.

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Published: Mar 20, 2017
Vol/Issue: 7(1)
License: View

Authors

Christopher R. Sutton

Division of Molecular Bioscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia

Cite This Article

Wen Juan Tu, Kristine Hardy, Christopher R. Sutton, et al. (2017). Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells. Scientific Reports, 7(1). https://doi.org/10.1038/srep44825

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

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