%0 Journal Article
%T Tissue-specific alteration of gene expression and function by RU486 and the GeneSwitch system
%A David Finkelstein
%A Fabio Demontis
%A Liam C. Hunt
%A Maricela Robles-Murguia
%A Yiping Fan
%J Archive of "NPJ Aging and Mechanisms of Disease".
%D 2019
%R 10.1038/s41514-019-0036-8
%X Transcriptional and functional defects induced by RU486 in skeletal muscle. a RNA-seq of thoracic skeletal muscle from Drosophila Act88F-GS flies treated with 100£¿¦ÌM RU486 for 10 days and untreated controls (¨CRU). RU486 represses the expression of nuclear-encoded mitochondrial genes, which is the first category of genes downregulated by RU486 (b). The transcriptome and the totality of mitochondrial genes are shown in gray and blue, respectively. The x axis reports the log ratio of gene expression changes of RU486-treated flies versus untreated controls, whereas the y axis reports the significance score, which is the ¨Clog10(P-value). Hence, values above the red line (P£¿<£¿0.05) correspond to significantly regulated genes. No GO categories are identified in genes with RU486-upregulated expression. c RU486 treatment decreases SDH activity in the muscle of Act88F-GS-Gal4 flies (n£¿=£¿4, SD, *P£¿<£¿0.05). d qRT-PCR analysis of skeletal muscle from Act88-GS-Gal4 flies treated with RU486. Consistent with RNA-seq data, qPCR analysis confirms that the expression of mitochondrial genes (CG10924, CG30493, CG41128, Hsp60, Las, and mRpS5) declines in response to RU486 treatment in a dose-dependent manner. Conversely, RU486 induces the expression of the cytoplasmic chaperones Hsp26 and Hsp83 (n£¿=£¿3, SD, *P£¿<£¿0.05). e In flies with muscle expression of GS-Gal4 (Mhc-GS-Gal4 and Act88F-Gs-Gal4), treatment for 1 week with 1, 10 or 100£¿¦ÌM RU486 leads to high percentages of flightless flies, compared with untreated controls. However, RU486 exerts minimal influence on the flight capacity of WT strains (w1118 and B3) and non-muscle GS-Gal4 strains with little or no GS-Gal4 expression in skeletal muscle (Act5c-GS-Gal4; FB-GS-Gal4, a combination of S32-GS-Gal4£¿+£¿S106-GS-Gal4). Supplementary Table 1 reports statistical analyse
%K Genome
%K Medical research
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529481/