Histone Acyl Code in Precision Oncology: Mechanistic Insights from Dietary and Metabolic Factors.

Cancer etiology involves complex interactions between genetic and non-genetic factors, with epigenetic mechanisms serving as key regulators at multiple stages of pathogenesis. Poor dietary habits contribute to cancer predisposition by impacting DNA methylation patterns, non-coding RNA expression, and histone epigenetic landscapes. Histone post-translational modifications (PTMs), including acyl marks, act as a molecular code and play a crucial role in translating changes in cellular metabolism into enduring patterns of gene expression.

Metabolomics of Acute vs. Chronic Spinach Intake in an Apc-Mutant Genetic Background: Linoleate and Butanoate Metabolites Targeting HDAC Activity and IFN-γ Signaling.

There is growing interest in the crosstalk between the gut microbiome, host metabolomic features, and disease pathogenesis. The current investigation compared long-term (26 week) and acute (3 day) dietary spinach intake in a genetic model of colorectal cancer. Metabolomic analyses in the polyposis in rat colon (Pirc) model and in wild-type animals corroborated key contributions to anticancer outcomes by spinach-derived linoleate bioactives and a butanoate metabolite linked to increased α-diversity of the gut microbiome.

GREB1: An evolutionarily conserved protein with a glycosyltransferase domain links ERα glycosylation and stability to cancer.

What covalent modifications control the temporal ubiquitination of ERα and hence the duration of its transcriptional activity remain poorly understood. We show that GREB1, an ERα-inducible enzyme, catalyzes O-GlcNAcylation of ERα at residues T553/S554, which stabilizes ERα protein by inhibiting association with the ubiquitin ligase ZNF598. Loss of GREB1-mediated glycosylation of ERα results in reduced cellular ERα levels and insensitivity to estrogen.

Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy.

Aberrant promoter DNA hypermethylation is a typical characteristic of cancer and it is often seen in malignancies. Recent studies showed that regulatory cis-elements found up-stream of many tumor suppressor gene promoter CpG island (CGI) attract DNA methyltransferases (DNMT) that hypermethylates and silence the genes. As epigenetic alterations are potentially reversible, they make attractive targets for therapeutic intervention.