Project description:General intelligence (g) is a common core shared by cognitive tasks. To study epigenetic regulation of “g”, 41 inbred mice raised under similar environmental conditions were subjected to five behavioral tests. We used principal component analysis to analyze 11 parameters that measure performance and reflect cognition of mice. Microarray gene expression analysis by using hippocampal RNAs of the 5, 12, and 8 mice consistently classified as having high, medium, and low cognition, respectively, by PC1 score and IQ score identified 17 genes that showed at least 1.3-fold difference in expression between mice with high and low cognition (FDR<0.30). Two of these genes were down-regulated and 15 of these genes were up-regulated in the high cognitive mice. Subsequent pathway-based analysis further identified gene-sets (GS) enriched in high cognitive mice and GS enriched in low cognitive mice. A number of genes implicated in our study have been previously associated with cognitive impairments. Our findings provide insights into genes and pathways regulated by epigenetic mechanisms in determining “g” and may shed lights on various disorders that affect cognitive function.
Project description:During hematopoiesis, cells originating from the same stem cell reservoir differentiate into distinct cell types. The mechanisms enabling common progenitors to differentiate into distinct cell fates are not fully understood. Here, we identify chromatin-regulating and cell-fate-determining transcription factors (TF) governing dendritic cell (DC) development by annotating the enhancer and promoter landscapes of the DC lineage. Combining these analyses with detailed over-expression, knockdown and ChIP-Seq studies, we show that Irf8 functions as a plasmacytoid DC epigenetic and fate-determining TF, regulating massive, cell-specific chromatin changes in thousands of pDC enhancers. Importantly, Irf8 forms a negative feedback loop with Cebpb, a monocyte-derived DC epigenetic fate-determining TF. We show that using this circuit logic, differential activity of TF can stably define epigenetic and transcriptional states, regardless of the microenvironment. More broadly, our study proposes a general paradigm that allows closely related cells with a similar set of signal-dependent factors to generate differential and persistent enhancer landscapes. Here we profiled accessible chromatin of moDC and pDC using ATAC-seq assay, developed by Buenrostro et al. (2013)
Project description:We report the application of mRNA sequencing technology for identifying that the genetic linkage of higher intelligence with longevity in Drosophilla melanogaster. a transcriptome analysis was performed by sequencing the total mRNA. The differentially expressed gene analysis by a negative binomial test showed that a subset of genes displayed remarkably altered expression where 56, 152, and 26 genes were significantly upregulated (adjusted P value <0.01), and 30, 397, and 10 genes were downregulated (adjusted P value < 0.01) in INT compared to F0, NINT compared to F0, and INT compared to NINT each. The functions of the differentially expressed genes were analyzed at high levels by using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment program. Compared to F0, the pathways of ribosome and autophagy were up-regulated in INT while the pathways related to metabolisms were down-regulated. Meanwhile, the pathways associated with genome stability and immune reaction was upregulated and the pathway of oxidative phosphorylation responsible for ATP generation was down regulated in NINT. The KEGG comparison of INT with NINT, which eliminates genes associated with the environmental factors during the selection process, visualized more precise pathways associated with higher intelligence and longevity. The pathways related to genome stability (Fanconi anemia pathway, Mismatch repair, DNA replication, Homologous recombination, and Nucleotide excision repair) and immune reaction (Toll and lmd signaling pathway) were up-regulated in NINT, and these pathways were down-regulated in INT.
Project description:The aim of this study is to do a side-by-side comparison of the transcriptomes that are regulated under Cu and Cd stress at the early stage in rice roots. The comparison of transcriptomes between Cu and Cd treatments and the application of bioinformatics procedures (e.g. regulated gene analysis) are potentially useful approaches for determining the both general and individual early responses triggered by each metal. Identify genes and pathways that would discriminate among the actions of Cu and Cd.
Project description:The general objectives are to evaluate activity and the safety of regorafenib in a population of patients bearing advanced, refractory colorectal cancers and to explore the different downstream molecular pathways to identify tumor response and resistance mechanisms.
Project description:Stable changes in chromatin states and gene expression in cells of the immune system form the basis for their memory of infections and other challenges. We used naturally occurring cis-regulatory variation in wild-derived inbred mouse strains to explore the mechanisms underlying long-lasting vs. transient gene regulation in antigen-specific CD8 T cells responding to acute viral infection. Our observations provide novel insights into the mechanisms driving stable and reversible transcriptional and epigenetic memory in virus-specific CD8 T cells. These findings suggest a general mechanism for the formation of epigenetic memory in CD8 T cells and other immune and non-immune cells.