Project description:Transcriptional profiling by array of CML CD34+ cells to understand the response of chronic myeloid leukaemia stem cells to an EZH2 inhibitor, GSK343.
Project description:We developed and performed LIMe-Hi-C in order to assess lamina association, DNA methylation, and chromosome conformation in one experimental workflow. We combined LIMe-Hi-C with chemcial inhibition of EZH2 and DNMT1 to better understand the influence of H3K27me3 and DNA methylation on 3D genome organization.
Project description:The study evaluated the differential gene expression in A375 cells treated with DMSO when compared to XL413 or GSK343 or GSK343 and XL413 combination using RNA-seq
Project description:K562 cell line treated with 1,6-HD and proteins were captured via cross-linking. We quantified chromatin structure changes and chromatin binding proteins in K562 cell before and after 1,6-hexanediol treatment by Hi-C and Hi-MS, respectively.
Project description:Background: Witches’ broom disease of Mexican lime (Citrus aurantifolia L.), which is caused by the phytoplasma “Candidatus Phytoplasma aurantifolia”, is a devastating disease that results in significant economic losses. Plants adapt to abiotic stresses by regulating gene expression at the transcriptional and post-transcriptional levels. MicroRNAs (miRNAs) are a recently identified family of molecules that regulate plant responses to environmental stresses through post-transcriptional gene silencing. Methods: Using a high-throughput approach to sequence small RNAs, we compared the expression profiles of miRNAs in healthy Mexican lime trees and in plants infected with “Ca. Phytoplasma aurantifolia”. Results: Our results demonstrated the involvement of different miRNAs in the response of Mexican lime trees to infection by “Ca. Phytoplasma aurantifolia”. We identified miRNA families that are expressed differentially upon infection with phytoplasmas. Most of the miRNAs had variants with small sequence variations (isomiRs), which are expressed differentially in response to pathogen infection. Conclusions: It is likely that the miRNAs that are expressed differentially in healthy and phytoplasma-infected Mexican lime trees are involved in coordinating the regulation of hormonal, nutritional, and stress signalling pathways, and the complex interactions between them. Future research to elucidate the roles of these miRNAs should improve our understanding of the level of diversity of specific plant responses to phytoplasmas.
Project description:The study evaluated the differential gene expression in control Antibody or Ant-CXCL10 antibody injected mouse when compared to EZH2 inhibitor GSK343 treated mice tumors Briefly, control Antibody or Ant-CXCL10 antibody injected C57BL/6 mouse were treated with or without GSK343were analyzed for RNA-seq
Project description:We developed and performed LIMe-ID to simultaneously measure lamina association and DNA methylation in one experimental workflow. We then conducted LIMe-ID following perturbations of PRC2 to better understand the influence of H3K27me3 on lamina association.
Project description:Schistosomiasis is a chronic and debilitating disease caused by a trematode of the genus Schistosoma. The current strategy for the control of the disease involves treatment with Praziquantel, the only available drug. The development of new drugs is therefore a top priority. Drugs that inhibit histone modifying enzymes have been used in cancer, altering gene expression, replication, repair and DNA recombination. Schistosoma parasites have some characteristics similar to malignant tumors, such as intense cell division and high levels of metabolic activity. Here we evaluate in Schistosoma mansoni the effect of GSK343, an inhibitor of the histone methyltransferase EZH2 that had been shown to arrest or reduce the growth of human cancer cells. We show that GSK343 causes damage to the parasite tegument and reduces egg laying in vitro, concomitant with a decrease in levels of H3K27me3, the histone mark put in place by EZH2. RNA-seq and proteomic analyses of treated parasites showed changes in the expression of hundreds of genes involved in important metabolic processes. In females, a marked decrease was observed in the expression of genes related to processes such as DNA replication and noncoding RNA metabolism. In conclusion, the histone methyltransferase EZH2 seems to be a promising novel drug target against schistosomiasis.