Intracellular growth of Chlamydia trachomatis leads to global histone hypermethylation by impairing demethylation
Abstract
, an intracellular bacterium, hijacks metabolites from the host cell for its own proliferation. We provide evidence of global hypermethylation of the host proteome, including histones during the late stages of infection. Single-cell analyses revealed co-occurrence of several methylated residues on histones while infection did not alter S-adenosylmethionine levels. Histone hypermethylation correlated positively with bacterial load and was prevented by antibiotic treatment. Mapping of trimethylation of histone 3 at residues K4 and K9 revealed a broad distribution throughout chromatin. Nuclear fractions of infected cells exhibited a fourfold decrease in demethylase activity against H3K4me3 and a twofold increase in succinate concentration, a competitive inhibitor for the demethylase co-factor α-ketoglutarate. Supplementation of the culture medium with dimethyl-ketoglutarate (DMKG) or with iron, a second co-factor of histone lysine demethylases, reduced histone hypermethylation. DMKG supplementation modified the transcription of about one third of the infection-responsive genes, indicating that histone hypermethylation contributes to modulating the transcriptional response of the host to infection. Finally, chemical inhibition of histone demethylases in a mouse model of infection showed a moderate benefit regarding the outcome of infection. Overall, our data show that the metabolic pressure exerted by a pathogen with an intracellular lifestyle drives epigenetic changes in infected cells.
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BibTeX
@article{charendoff2026intracellular,
title = {{Intracellular growth of Chlamydia trachomatis leads to global histone hypermethylation by impairing demethylation}},
author = {Chloé Charendoff and Félix Louchez and Yongzheng Wu and Lee Dolat and Guillaume Velasco and Stéphanie Perrinet and Adrian Gabriel Torres and Laure Blanchet and Magalie Duchateau and Quentin Giai Gianetto and Mariette Matondo and Laurence del Maestro and Slimane Ait-Si-Ali and Frédéric Bonhomme and Gaël Millot and Vannary Meas-Yedid and Lluís Ribas de Pouplana and Elisabeth Martinez and Raphael Valdivia and Agathe Subtil},
journal = {eLife},
year = {2026},
month = sep,
doi = {10.7554/elife.110111},
url = {https://hal.science/hal-05762609v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Intracellular growth of Chlamydia trachomatis leads to global histone hypermethylation by impairing demethylation
AU - Chloé Charendoff
AU - Félix Louchez
AU - Yongzheng Wu
AU - Lee Dolat
AU - Guillaume Velasco
AU - Stéphanie Perrinet
AU - Adrian Gabriel Torres
AU - Laure Blanchet
AU - Magalie Duchateau
AU - Quentin Giai Gianetto
AU - Mariette Matondo
AU - Laurence del Maestro
AU - Slimane Ait-Si-Ali
AU - Frédéric Bonhomme
AU - Gaël Millot
AU - Vannary Meas-Yedid
AU - Lluís Ribas de Pouplana
AU - Elisabeth Martinez
AU - Raphael Valdivia
AU - Agathe Subtil
PY - 2026
DA - 2026/09/14
JO - eLife
DO - 10.7554/elife.110111
UR - https://hal.science/hal-05762609v1
AB - , an intracellular bacterium, hijacks metabolites from the host cell for its own proliferation. We provide evidence of global hypermethylation of the host proteome, including histones during the late stages of infection. Single-cell analyses revealed co-occurrence of several methylated residues on histones while infection did not alter S-adenosylmethionine levels. Histone hypermethylation correlated positively with bacterial load and was prevented by antibiotic treatment. Mapping of trimethylation of histone 3 at residues K4 and K9 revealed a broad distribution throughout chromatin. Nuclear fractions of infected cells exhibited a fourfold decrease in demethylase activity against H3K4me3 and a twofold increase in succinate concentration, a competitive inhibitor for the demethylase co-factor α-ketoglutarate. Supplementation of the culture medium with dimethyl-ketoglutarate (DMKG) or with iron, a second co-factor of histone lysine demethylases, reduced histone hypermethylation. DMKG supplementation modified the transcription of about one third of the infection-responsive genes, indicating that histone hypermethylation contributes to modulating the transcriptional response of the host to infection. Finally, chemical inhibition of histone demethylases in a mouse model of infection showed a moderate benefit regarding the outcome of infection. Overall, our data show that the metabolic pressure exerted by a pathogen with an intracellular lifestyle drives epigenetic changes in infected cells.
SN - 2050-084X
ER -