Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes - SIMPA - Laboratoire Stress, IMmunité, PAthogènes Accéder directement au contenu
Article Dans Une Revue International Journal of Molecular Sciences Année : 2022

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

Résumé

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× g 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× g 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.

Domaines

Immunologie

Dates et versions

hal-03909559 , version 1 (21-12-2022)

Identifiants

Citer

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, 2022, 23 (13), pp.7133. ⟨10.3390/ijms23137133⟩. ⟨hal-03909559⟩
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