Project description:Mutating esc (extra sex-combs), maternal and zygotic, leads to loss of H3K27me3 and affects Hox-patterning along the AP-axis in neurogenesis
Project description:To dissect the significance underlying the delay between Hox transcription and translation, we profiled global Hox gene expression using an in vitro ESC-derived motor neuron differentiation system
Project description:Parents transmit genetic and epigenetic information to their offspring. Maternal effect genes regulate the offspring epigenome to ensure normal development. Here we report that the epigenetic regulator SMCHD1 has a maternal effect on Hox gene expression and skeletal patterning. Maternal SMCHD1, present in the oocyte and preimplantation embryo, prevents precocious activation of Hox genes post-implantation. Without maternal SMCHD1, highly penetrant posterior homeotic transformations occur in the embryo. Hox genes are decorated with Polycomb marks H2AK119ub and H3K27me3 from the oocyte throughout early embryonic development; however, loss of maternal SMCHD1 does not deplete these marks. Therefore, we propose maternal SMCHD1 acts downstream of Polycomb marks to establish a chromatin state necessary for persistent epigenetic silencing and appropriate Hox gene expression later in the developing embryo. This is a striking role for maternal SMCHD1 in long-lived epigenetic effects impacting offspring phenotype.
Project description:This phase I trial is studying the best dose of 3-AP and the side effects of giving 3-AP together with gemcitabine in treating patients with advanced solid tumors or lymphoma. Drugs used in chemotherapy, such as 3-AP and gemcitabine (GEM), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 3-AP may help gemcitabine kill more cancer cells by making the cells more sensitive to the drug. 3-AP may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Project description:Comparison of transcription profiles on anterior tectum and posterior tectum at HH35 an HH37, and that of medial and lateral tectum at HH30 and HH35. The goal was to obtain summary of genes expressed differentially across the AP and DV axis.
Project description:During Drosophila development, Polycomb-group and Trithorax-group proteins function to ensure correct maintenance of transcription patterns by epigenetically repressing or activating target gene expression. To get a deep insight into the PcG and trxG pathways, we investigated a BRCT domain-containing protein called PTIP, which was generally identified as a transcriptional coactivator and belongs to the TRR complex. At the genome scale, we sorted given PTIP binding peaks into two groups: PTIP/TRR-cobound and PTIP/PC-cobound peaks. In particular, we found that PTIP mediates the molecular switch between H3K4me3/H3K27ac and H3K27me3 histone modifications at TRR or PC occupied regions. Thus, we suggest that PTIP is a mediator rather than a dedicated co-activator along PcG and trxG pathways. Our hypothesis is further supported by the genetic assay: PTIP interacts genetically with either PcG or TrxG in a dosage-dependent manner, suggesting that PTIP functions as a co-factor of PcG/TrxG proteins. In addition, in accordance with the analysis of ChIP-seq, these genetic interactions correlate with modified ectopic HOX protein levels in imaginal discs, which reveals an essential role for PTIP in PcG-mediated Hox gene repression. Hence, we reveal a novel role for PTIP in the epigenetic regulation of gene expression along PcG and trxG pathways.
Project description:We have carried out a systematic analysis of the in vivo genomic binding profiles of all eight Drosophila Hox proteins using transient transfection in Kc167 cells to examine Hox protein targeting. In addition, we have examined Hox protein binding in cells transfected with both Hox and the cofactor, Homothorax. Provision of Homothorax also recruits the cofactor Extradenticle.