Telomeric Heterochromatin Propagation and Histone Acetylation Control Mutually Exclusive Expression of Antigenic Variation Genes in Malaria Parasites

SummaryMalaria parasites use antigenic variation to avoid immune clearance and increase the duration of infection in the human host. Variation at the surface of P. falciparum-infected erythrocytes is mediated by the differential control of a family of surface antigens encoded by var genes. Switching of var gene expression occurs in situ, mostly from telomere-associated loci, without detectable DNA alterations, suggesting that it is controlled by chromatin structure. We have identified chromatin modifications at telomeres that spread far into telomere-proximal regions, including var gene loci (>50 kb). One type of modification is mediated by a protein homologous to yeast Sir2 called PfSir2, which forms a chromosomal gradient of heterochromatin structure and histone hypoacetylation. Upon activation of a specific telomere-associated var gene, PfSir2 is removed from the promoter region and acetylation of histone occurs. Our data demonstrate that mutually exclusive transcription of var genes is linked to the dynamic remodeling of chromatin

Fe de errores de “Evaluation of the TRPM2 channel as a biomarker in breast cancer using public databases analysis”

Background: Breast cancer is one of the most common malignancies affecting women. Recent investigations have revealed a major role of ion channels in cancer. The transient receptor potential melastatin-2 (TRPM2) is a plasma membrane and lysosomal channel with important roles in cell migration and cell death in immune cells and tumor cells. Methods: In this study, we investigated the prognostic value of TRPM2 channel in breast cancer, analyzing public databases compiled in OncomineTM (Thermo Fisher, Ann Arbor, MI) and online Kaplan-Meier Plotter platforms. Results: The results revealed that TRPM2 mRNA overexpression is significant in situ and invasive breast carcinoma compared to normal breast tissue. Furthermore, multi-gene validation using OncomineTM showed that this channel is coexpressed with proteins related to cellular migration, transformation, and apoptosis. On the other hand, Kaplan-Meier analysis exhibited that low expression of TRPM2 could be used to predict poor outcome in ER- and HER2+ breast carcinoma patients. Conclusions: TRPM2 is a promising biomarkerfor aggressiveness of breast cancer, and a potential target for the development of new therapies