Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes

Gravity changes are major stressors encountered during spaceflight that affect the immune system. We previously evidenced that hypergravity exposure during gestation affects the TCRβ repertoire of newborn pups. To identify the mechanisms underlying this observation, we studied post-translational his...

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Main Authors: Gaetano Calcagno, Nassima Ouzren, Sandra Kaminski, Stéphanie Ghislin, Jean-Pol Frippiat
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/13/7133
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author Gaetano Calcagno
Nassima Ouzren
Sandra Kaminski
Stéphanie Ghislin
Jean-Pol Frippiat
author_facet Gaetano Calcagno
Nassima Ouzren
Sandra Kaminski
Stéphanie Ghislin
Jean-Pol Frippiat
author_sort Gaetano Calcagno
collection DOAJ
description Gravity changes are major stressors encountered during spaceflight that affect the immune system. We previously evidenced that hypergravity exposure during gestation affects the TCRβ repertoire of newborn pups. To identify the mechanisms underlying this observation, we studied post-translational histone modifications. We first showed that among the four studied post-translational histone H3 modifications, only lysine 27 trimethylation (H3K27me3) is downregulated in the thymus of mice exposed to 2× <i>g</i> for 21 days. We then asked whether the TCRβ locus chromatin structure is altered by hypergravity exposure. ChIP studies performed on four Vβ segments of the murine double-negative SCIET27 thymic cell line, which corresponds to the last maturation stage before V(D)J recombination, revealed increases in H3K27me3 after 2× <i>g</i> exposure. Finally, we evaluated the implication for the EZH2 methyltransferase in the regulation of the H3K27me3 level at these Vβ segments by treating SCIET27 cells with the GSK126-specific inhibitor. These experiments showed that the downregulation of H3K27me3 contributes to the regulation of the Vβ germline transcript expression that precedes V(D)J recombination. These data show that modifications of H3K27me3 at the TCRβ locus likely contribute to an explanation of why the TCR repertoire is affected by gravity changes and imply, for the first time, EZH2 in the regulation of the TCRβ locus chromatin structure.
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spelling doaj.art-0f2e3f9c2cd0428494990006f4a6f0162023-11-23T20:08:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313713310.3390/ijms23137133Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine ThymocytesGaetano Calcagno0Nassima Ouzren1Sandra Kaminski2Stéphanie Ghislin3Jean-Pol Frippiat4Stress, Immunity, Pathogens Laboratory, SIMPA, Université de Lorraine, F-54000 Nancy, FranceStress, Immunity, Pathogens Laboratory, SIMPA, Université de Lorraine, F-54000 Nancy, FranceStress, Immunity, Pathogens Laboratory, SIMPA, Université de Lorraine, F-54000 Nancy, FranceStress, Immunity, Pathogens Laboratory, SIMPA, Université de Lorraine, F-54000 Nancy, FranceStress, Immunity, Pathogens Laboratory, SIMPA, Université de Lorraine, F-54000 Nancy, FranceGravity changes are major stressors encountered during spaceflight that affect the immune system. We previously evidenced that hypergravity exposure during gestation affects the TCRβ repertoire of newborn pups. To identify the mechanisms underlying this observation, we studied post-translational histone modifications. We first showed that among the four studied post-translational histone H3 modifications, only lysine 27 trimethylation (H3K27me3) is downregulated in the thymus of mice exposed to 2× <i>g</i> for 21 days. We then asked whether the TCRβ locus chromatin structure is altered by hypergravity exposure. ChIP studies performed on four Vβ segments of the murine double-negative SCIET27 thymic cell line, which corresponds to the last maturation stage before V(D)J recombination, revealed increases in H3K27me3 after 2× <i>g</i> exposure. Finally, we evaluated the implication for the EZH2 methyltransferase in the regulation of the H3K27me3 level at these Vβ segments by treating SCIET27 cells with the GSK126-specific inhibitor. These experiments showed that the downregulation of H3K27me3 contributes to the regulation of the Vβ germline transcript expression that precedes V(D)J recombination. These data show that modifications of H3K27me3 at the TCRβ locus likely contribute to an explanation of why the TCR repertoire is affected by gravity changes and imply, for the first time, EZH2 in the regulation of the TCRβ locus chromatin structure.https://www.mdpi.com/1422-0067/23/13/7133hypergravitystressT lymphopoiesisV(D)J recombinationepigeneticEZH2
spellingShingle Gaetano Calcagno
Nassima Ouzren
Sandra Kaminski
Stéphanie Ghislin
Jean-Pol Frippiat
Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes
International Journal of Molecular Sciences
hypergravity
stress
T lymphopoiesis
V(D)J recombination
epigenetic
EZH2
title Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes
title_full Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes
title_fullStr Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes
title_full_unstemmed Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes
title_short Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes
title_sort chronic hypergravity induces a modification of histone h3 lysine 27 trimethylation at tcrβ locus in murine thymocytes
topic hypergravity
stress
T lymphopoiesis
V(D)J recombination
epigenetic
EZH2
url https://www.mdpi.com/1422-0067/23/13/7133
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