Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation

Abstract T-cell activation induces context-specific gene expression programs that promote energy generation and biosynthesis, progression through the cell cycle and ultimately cell differentiation. The aim of this study was to apply the omni ATAC-seq method to characterize the landscape of chromatin...

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Autores principales:	Muhammad Munir Iqbal, Michael Serralha, Parwinder Kaur, David Martino
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3859313a63344269ae36ced77d5863b4
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spelling	oai:doaj.org-article:3859313a63344269ae36ced77d5863b42021-12-02T15:39:41ZMapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation10.1038/s41598-021-93509-w2045-2322https://doaj.org/article/3859313a63344269ae36ced77d5863b42021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93509-whttps://doaj.org/toc/2045-2322Abstract T-cell activation induces context-specific gene expression programs that promote energy generation and biosynthesis, progression through the cell cycle and ultimately cell differentiation. The aim of this study was to apply the omni ATAC-seq method to characterize the landscape of chromatin changes induced by T-cell activation in mature naïve CD4+ T-cells. Using a well-established ex vivo protocol of canonical T-cell receptor signaling, we generated genome-wide chromatin maps of naïve T-cells from pediatric donors in quiescent or recently activated states. We identified thousands of individual chromatin accessibility peaks that are associated with T-cell activation, the majority of which were annotated intronic and intergenic enhancer regions. A core set of 3268 gene promoters underwent chromatin remodeling and concomitant changes in gene expression in response to activation, and were enriched in multiple pathways controlling cell cycle regulation, metabolism, inflammatory response genes and cell survival. Leukemia inhibitory factor (LIF) was among those factors that gained the highest accessibility and expression, in addition to IL2-STAT5 dependent chromatin remodeling in the T-cell activation response. Using publicly available data we found the chromatin response was far more dynamic at 24-h compared with 72-h post-activation. In total 546 associations were reproduced at both time-points with similar strength of evidence and directionality of effect. At the pathways level, the IL2-STAT5, KRAS signalling and UV response pathways were replicable at both time-points, although differentially modulated from 24 to 72 h post-activation.Muhammad Munir IqbalMichael SerralhaParwinder KaurDavid MartinoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Muhammad Munir Iqbal Michael Serralha Parwinder Kaur David Martino Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation
description	Abstract T-cell activation induces context-specific gene expression programs that promote energy generation and biosynthesis, progression through the cell cycle and ultimately cell differentiation. The aim of this study was to apply the omni ATAC-seq method to characterize the landscape of chromatin changes induced by T-cell activation in mature naïve CD4+ T-cells. Using a well-established ex vivo protocol of canonical T-cell receptor signaling, we generated genome-wide chromatin maps of naïve T-cells from pediatric donors in quiescent or recently activated states. We identified thousands of individual chromatin accessibility peaks that are associated with T-cell activation, the majority of which were annotated intronic and intergenic enhancer regions. A core set of 3268 gene promoters underwent chromatin remodeling and concomitant changes in gene expression in response to activation, and were enriched in multiple pathways controlling cell cycle regulation, metabolism, inflammatory response genes and cell survival. Leukemia inhibitory factor (LIF) was among those factors that gained the highest accessibility and expression, in addition to IL2-STAT5 dependent chromatin remodeling in the T-cell activation response. Using publicly available data we found the chromatin response was far more dynamic at 24-h compared with 72-h post-activation. In total 546 associations were reproduced at both time-points with similar strength of evidence and directionality of effect. At the pathways level, the IL2-STAT5, KRAS signalling and UV response pathways were replicable at both time-points, although differentially modulated from 24 to 72 h post-activation.
format	article
author	Muhammad Munir Iqbal Michael Serralha Parwinder Kaur David Martino
author_facet	Muhammad Munir Iqbal Michael Serralha Parwinder Kaur David Martino
author_sort	Muhammad Munir Iqbal
title	Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation
title_short	Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation
title_full	Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation
title_fullStr	Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation
title_full_unstemmed	Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation
title_sort	mapping the landscape of chromatin dynamics during naïve cd4+ t-cell activation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3859313a63344269ae36ced77d5863b4
work_keys_str_mv	AT muhammadmuniriqbal mappingthelandscapeofchromatindynamicsduringnaivecd4tcellactivation AT michaelserralha mappingthelandscapeofchromatindynamicsduringnaivecd4tcellactivation AT parwinderkaur mappingthelandscapeofchromatindynamicsduringnaivecd4tcellactivation AT davidmartino mappingthelandscapeofchromatindynamicsduringnaivecd4tcellactivation
_version_	1718385865828335616

Mapping the landscape of chromatin dynamics during naïve CD4+ T-cell activation

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