Project description:The CpG island methylator phenotype (CIMP) is associated with prognosis and drug sensitivity in multiple cancer types. In gastric cancer, the CIMP is closely associated with Epstein-Barr virus (EBV) infection and AT-rich interactive domain 1A (ARID1A) mutations, a component of the SWI/SNF chromatin remodeling complex. However, the involvement of SWI/SNF defects in CIMP induction has been unclear. In this study, we demonstrate a causal role of ARID1A loss-of-function in CIMP induction. Mutations of SWI/SNF components, especially ARID1A, was associated with the CIMP, as well as EBV infection, in gastric cancers, and also in uterine endometrial and colorectal cancers, which are not affected by EBV infection. Genome-wide DNA methylation analysis showed that ARID1A knockout (KO) in cultured 293FT cells and gastric epithelial cells, GES1, induced aberrant DNA methylation of a substantial number of CpG sites. DNA methylation was induced at genomic regions with high levels of pre-existing histone H3 lysine 27 trimethylation (H3K27me3) and those with acquired H3K27me3 by ARID1A KO. These results showed that the ARID1A mutation induced aberrant DNA methylation, and this is likely to be one of the potential mechanisms of CIMP induction. (See GSE188293 for data of GES1 with ARID1A KO.)
Project description:To investigate whether rat adult hepatocytes would exhibit different characteristics dependent on their ploidy statuses, we compared the transcriptome profile of 2c, 4c and 8c hepatocytes by mRNA microarray.
Project description:Hyperinsulinemia affects 72% of Fanconi anemia (FA) patients and an additional 25% experience lowered glucose tolerance or frank diabetes. The underlying molecular mechanisms contributing to the dysfunction of FA pancreas β cells is unknown. These experiments were performed in 293FT HEK cells as a part of the optimization and validation of the endogenous IP and to establish the FANCA interactome in a non-pancreas cell line to delineate beta cell-specific FANCA interactions.
Project description:Undifferentiated FM95-14 human embryonic myoblasts contain myogenic stem/progenitor cells. Gene expression analysis and comparison to FM95-14 cells that have been allowed to differentiate will allow the ascertainment of genes that are implicated in myogenic lineage commitment. Human myoblast were also differentiated for 4 days. 293FT-human embroynal kidney were used as a human control cell line for human myoblast study. Experiment Overall Design: this experiment include 3 samples (293FT-human embroynal kidney, undifferentiated FM95-14 myoblast, and differentiated myoblast) with 3 replicates on 2 platforms for a total of 18 Samples.
Project description:We generated tetracycline-inducible myc-GABPα-expressing Gabpα conditional knockout embryonic stem cells (Tet-Gabbpα cKO ES cells), and then compared the transcriptional profiles between control (-Tet) and Gabpα-null (+Tet) cells by an oligo DNA microarray analysis.