Project description:AP2-FG is a female-specific transcription factor (TF) that plays an essential role in female gametocyte development. AP2-FG activates hundreds of genes by binding to a female-specific ten-base cis-acting element. Here, we report that in the rodent malaria parasite Plasmodium berghei, another female-specific TF designated as a partner of AP2-FG (PFG), controls gene expression in female gametocytes cooperatively with AP2-FG. Transcriptional mechanisms were analyzed in Plasmodium berghei female gametocytes.
Project description:AP2-FG is a female-specific transcription factor (TF) that plays an essential role in female gametocyte development. AP2-FG activates hundreds of genes by binding to a female-specific ten-base cis-acting element. Here, we report that in the rodent malaria parasite Plasmodium berghei, another female-specific TF designated as a partner of AP2-FG (PFG), controls gene expression in female gametocytes cooperatively with AP2-FG. Transcriptional mechanisms were analyzed in Plasmodium berghei female gametocytes.
Project description:To understand the transcription regulation of HIF1α in kidney tubule cells, we stabilized HIF1α with 50μM FG-4592 in HK2 cells. We captured ChIPseq of HIF1α and constructed transcription profile under FG-4592.
Project description:To investigate effects on mRNA expression through treatment with FG-3019, irradiation and their combination to gain mechanistic hypotheses on the effects of these treatments on glioblastoma stem cell like cells which have been observed in vitro and in vivo. mRNA expression was measured 6 h after treatment with FG-3019, irradiation and their combination. 3 biological replicates were analyzed for each treatment condition (control, FG-3019, irratiation and FG-3019+irradiation)
Project description:AP2-FG is a female-specific transcription factor (TF) that plays an essential role in female gametocyte development. AP2-FG activates hundreds of genes by binding to a female-specific ten-base cis-acting element. Here, we report that in the rodent malaria parasite Plasmodium berghei, another female-specific TF designated as a partner of AP2-FG (PFG), controls gene expression in female gametocytes cooperatively with AP2-FG.
Project description:Recurrent cancer-causing fusions of NUP98 produce higher-order assemblies known as condensates. How NUP98 oncofusion-driven condensates activate oncogenes remainspoorly understood. Here, we investigate NUP98-PHF23, a leukemogenic chimera of the FG-repeat region of NUP98 and the H3K4me3-binding PHD finger of PHF23. Our integrated analyses using mutagenesis, proteomics, genomics, and condensate reconstitution demonstrate that the PHD finger targets condensates to H3K4me3-demarcated developmental genes and the FG repeats determine condensate composition and gene activation. The FG repeats are necessary to form condensates that partition a specific set of transcriptional regulators, notably the MLL family of H3K4 methylation-writing enzymes and BRD4. The FG repeats are sufficient, when tethered to the genome, to partition these transcriptional regulators and activate genes. NUP98-PHF23 assembles chromatin-bound condensates that partition multiple positive regulators, initiating a feed-forward loop of reading-and-writing active histone modifications. This network of interactions enforces an open chromatin landscape at proto-oncogenes, thereby driving cancerous transcriptional programs.
Project description:Pancreatic ductal adenocarcinoma (PDA) is characterized by abundant desmoplasia and poor tissue perfusion. These features are proposed to limit access of therapies to neoplastic cells and blunt treatment efficacy. Indeed, several agents that target the PDA microenvironment promote chemotherapy delivery and improve anti-neoplastic responses in murine models of PDA. Here, we employed the FG-3019 monoclonal antibody directed against the pleiotropic matricellular signaling molecule connective tissue growth factor (CTGF/CCN2). FG-3019 treatment increased PDA cell killing and led to a dramatic tumor response without altering gemcitabine delivery. Microarray expression profiling revealed the down-regulation by FG-3019 of several anti-apoptotic transcripts, including the master regulator Xiap, down-regulation of which has been shown to sensitize PDA to gemcitabine. Decreases in XIAP protein by FG-3019 in the presence and absence of gemcitabine were confirmed by immunoblot, while increases in XIAP protein were seen in PDA cell lines treated with recombinant CTGF. Therefore, alterations in survival cues following targeting of tumor microenvironmental factors may play an important role in treatment responses in animal models and, by extension, PDA patients. Total RNA was isolated from KPC mouse PDA tumors 9 days after initiation of treatment with IgG (n=7 biological replicates), FG-3019 (n=5), IgG + gemcitabine (n=6), or FG-3019 + gemcitabine (n=6) and hybridized to Affymetrix 430A 2.0 microarrays. CEL files were processed by GC-RMA and rescaled using median per-gene normalization in GeneSpring GX 7.3.1.
Project description:Fungal effectors are key determinants of disease development, promoting pathogen growth and spreading in plant tissues. In the wheat/Fusarium graminearum (Fg) interaction determining the Fusarium Head Blight disease (FHB), the molecular bases of Fg aggressiveness remain widely unknown. The aim of this work is to provide a better understanding of Fusarium graminearum aggressiveness determinism during its interaction with bread wheat. Phenotyping in controlled conditions of three fungal strains was carried out on three wheat cultivars contrasted by their susceptibility to FHB. Qualitative and quantitative characterizations of the three strain's whole proteomes expressed in planta have been performed with special interest on effectors and proteins coded by Fg aggressiveness-related genes. Considering all fusaried wheat samples, this experimentation identified 615 unique Fg proteins, including 583 identified in all samples. Furthermore, 71 putative Fg effectors were found in the identified proteins. Among all the fungal proteins quantified, nearly 76% showed significant abundance differences between the Fg strains. Two-way ANOVA were computed to evaluate the contribution of the "Strain" and "Cultivar" factors on the Fg protein abundances. Abundances that were deemed significant to each factor enabled a categorization of the proteins according to the factor(s) that drive(s) the abundance differences. This included: (i) Fg proteins whose abundance differences were specifically explained by the genetic background of the strain (Strain factor, Strain_effect proteins), (ii) Fg proteins whose abundance differences were only explained by the genetic background of the host plant (Cultivar factor, Cultivar_effect proteins), (iii) Fg proteins whose abundance differences were explained by both factors (Strain+Cultivar proteins), and (iv) Fg proteins whose abundance differences observed between strains were dependent on the host cultivar (Strain×Cultivar proteins). Considering each factor individually, a total of 139 Strain_effect proteins, 82 Cultivar_effect proteins, 117 Strain+Cultivar proteins and 2 Strain×Cultivar proteins were identified.
Project description:Fusarium head blight (FHB) is a major disease of cereal crops caused by the fungus Fusarium graminearum (Fg). FHB affects the flowering heads (or spikes). This study compare the gene expression profile in wheat spikelets from the very susceptible spring wheat cultivar Roblin inoculated with either water (H2O), a Fg strain (GZ3639) producing the mycotoxin deoxynivalenol (+DON), or a GZ3639-derived Fg strain which has been inactivated at the Tri5 locus (-DON).
Project description:Multiple molecular tools and assays were deployed to compare the resistant variety Sumai3 with three regionally adapted Canadian cultivars, Stettler, Muchmore and FL62R1. Macroscopic and microscopic disease evaluation established the relative level of Type II FHB resistance of the four varieties and revealed that the F. graminearum (Fg) infection process displayed substantial temporal differences among organs. The rachis was found to play a critical role in preventing Fg spread within spikes. Large-scale, organ-specific RNA-seq at different times after Fg infection demonstrated that diverse defense mechanisms were expressed faster and more intensely in the spikelet of resistant varieties. The roles of plant hormones during the interaction of wheat with Fg was inferred based on the transcriptomic data obtained and the quantification of the major plant hormones. Salicylic acid and jasmonic acid were found to play predominantly positive roles in FHB resistance, whereas auxin and ABA were associated with susceptibility, and ethylene appeared to play a dual role during the interaction with Fg.