eLife: upcoming articles

Intracellular growth of Chlamydia trachomatis leads to global histone hypermethylation by impairing demethylation

asubtil@pasteur.fr (Adrian Gabriel Torres) — Mon, 14 Sep 2026 00:00:00 +0000

Chlamydia trachomatis, an intracellular bacterium, highjacks 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-adenosyl methionine 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 of demethylase activity against H3K4me3 and a twofold increase in succinate concentration, a competitive inhibitor for the demethylase co-factor a-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.

A novel prognostic score based on carbohydrate antigen 125, alpha-fetoprotein and carcinoembryonic antigen for Predicting postoperative prognosis in endometrial cancer: Results from a retrospective cohort study

yangh9@sj-hospital.org (Bo Wang) — Mon, 10 Aug 2026 00:00:00 +0000

Background: Endometrial cancer (EC) is a common gynecological malignancy with increasing incidence. While several serum biomarkers have been studied for EC, their combined prognostic value remains unclear. This study aimed to evaluate the prognostic significance of preoperative serum CA125, CA19-9, CA72-4, CEA, and AFP levels in EC patients and develop a risk score for predicting survival outcomes.

Prominin 1 and Tweety Homology 1 both induce extracellular vesicle formation

bell@molbio.mgh.harvard.edu (Arezu Monshizadeh) — Tue, 13 Aug 2024 00:00:00 +0000

Prominin-1 (Prom1) is a five-transmembrane-pass integral membrane protein that associates with curved regions of the plasma membrane. Prom1 interacts with membrane cholesterol and actively remodels the plasma membrane. Membrane bending activity is particularly evident in photoreceptors, where Prom1 loss-of-function mutations cause failure of outer segment homeostasis, leading to cone-rod retinal dystrophy (CRRD). The Tweety Homology (Ttyh) protein family has been proposed to be homologous to Prominin, but it is not known whether Ttyh proteins have an analogous membrane-bending function. Here, we characterize the membrane-bending activity of human Prom1 and Ttyh1 in native bilayer membranes. We find that Prom1 and Ttyh1 both induce formation of extracellular vesicles (EVs) in cultured mammalian cells and that the EVs produced are physically similar. Ttyh1 is more abundant in EV membranes than Prom1 and produces EVs with membranes that are more tubulated than Prom1 EVs. We further show that Prom1 interacts more stably with membrane cholesterol than Ttyh1 and that this may contribute to membrane bending inhibition in Prom1 EVs. Intriguingly, a loss-of-function mutation in Prom1 associated with CRRD induces particularly stable cholesterol binding. These experiments provide mechanistic insight into Prominin function in CRRD and suggest that Prom and Ttyh belong to a single family of functionally related membrane-bending, EV-generating proteins.