Project description:linc00598 is a nuclear localized long noncoding RNA which transcribed in downstream of FoxO1. Previous studies showed that several nuclear retained lncRNAs function as transcriptional regulators. To find out the function of linc00598 as a transcriptional regulator, we performed microarray analysis using linc00598 knock down stable HEK293t cells. The results showed that positive cell cycle regulation related genes including cyclin D2 were regulated transcriptionally by linc00598. It was also observed that knock down of linc00598 induces G0/G1 cell cycle arrest and inhibit proliferation. Therefore linc00598 represents a novel cell cycle regulatory lncRNA and may be involved in promoting transformation of human cells.
Project description:Ethanol inhibits the proliferation of neural stem cells in the fetal, adolescent, and adult brain. The consequences are cognitive deficits associated with fetal alcohol spectrum disorder and alcohol use disorder. We tested the hypothesis that ethanol affects progression through cell cycle checkpoints by differentially modifying transcriptional processes. Monolayer cultures of NS-5 neural stem cells were treated for 48 hr with the mitogenic agent FGF2 or the anti-mitogenic TGFβ1 in the absence or presence of ethanol. Cell cycle elongation was induced by a global down-regulation of genes involved in cell cycle progression, including the cyclin E system. Checkpoint regulation occurred downstream of p21 and Jun-oncogene signaling cascades. Thus, ethanol can affect cell cycle progression by altering transcript expression of strategic genes downstream of the G1/S checkpoint.
Project description:We knocked down NF-Y in two types of neuronal cells, neuro2a neuroblastoma cells and sorted brain striatal cells, and performed gene expression profiling. We found that the down-regulated genes preferentially contained NF-Y-binding motifs in their proximal promoters, and notably enriched genes related to ER functions rather than those for cell cycle. These are highly contrast to the profiling data of HeLa and embryonic stem cells in which distinct down-regulation of cell cycle-related genes was observed by NF-Y knockdown. Clustering analysis further identified several functional clusters where populations of the down-regulated genes were highly distinct. Further analyses using chromatin immunoprecipitation and RNA-seq data revealed that transcriptomic difference was not correlated with the DNA binding of NF-Y but with splicing of NF-YA. These data suggest that neuronal cells have a different type of transcriptome in which ER-related genes are dominantly modulated by NF-Y, and imply that NF-YA splicing alteration rather than DNA-binding preference could be involved in this cell type-specific gene modulation.