Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes
Abstract
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.
Related
- Juvenile social isolation induces gene expression alterations and histone modification dysregulations in nucleus accumbens (NAc) neurons of female mice
- Chronic plus binge ethanol feeding synergistically induces neutrophil infiltration and liver injury in mice: A critical role for E-selectin
- Chronic Alcohol Exposure Induces Persistent DNA Damage Response Signaling and Sensitizes Breast Epithelial Cells to PARP Inhibition
- Chronic exercise induces a pathway-dependent electrophysiological signature in the mouse hippocampus
- Chronic Sleep Disruption Activates the Transcriptional Unfolded Protein Response and Induces Compartment-Specific Proteomic Changes in Mice
BibTeX
@article{calcagno2026chronic,
title = {{Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes}},
author = {Gaetano Calcagno and Nassima Ouzren and Sandra Kaminski and Stéphanie Ghislin and Jean-Pol Frippiat},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms23137133},
url = {https://hal.univ-lorraine.fr/hal-03909559v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Chronic Hypergravity Induces a Modification of Histone H3 Lysine 27 Trimethylation at TCRβ Locus in Murine Thymocytes
AU - Gaetano Calcagno
AU - Nassima Ouzren
AU - Sandra Kaminski
AU - Stéphanie Ghislin
AU - Jean-Pol Frippiat
PY - 2026
DA - 2026/09/03
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms23137133
UR - https://hal.univ-lorraine.fr/hal-03909559v1
AB - 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.
SN - 1661-6596
SN - 1422-0067
ER -