Project description:Fumarate Hydratase (FH) is a mitochondrial enzyme that catalyses the reversible hydration of fumarate to malate in the TCA cycle. Germline mutations of FH lead to HLRCC, a cancer syndrome characterised by a highly aggressive form of renal cancer(1). Although HLRCC tumours metastasise rapidly, FH-deficient mice develop premalignant cysts in the kidneys, rather than carcinomas(2). How Fh1-deficient cells overcome these tumour suppressive events during transformation is unknown. Here, we perform a genome-wide CRISPR/Cas9 screen to identify genes that, when ablated, enhance the proliferation of Fh1-deficient cells. We found that the depletion of the HIRA enhances proliferation and invasion of Fh1-deficient cells in vitro and in vivo. Mechanistically, Hira loss enables the activation of MYC and its target genes, increasing nucleotide metabolism specifically in Fh1-deficient cells, independent of its histone chaperone activity. These results are instrumental for understanding mechanisms of tumorigenesis in HLRCC and the development of targeted treatments for patients.
Project description:We reported transcriptome profiles of rifamycin SV-produced strain Amycolatopsis mediterranei U32 in the Bennet medium with or without 80 mM nitrate in different cultivation stage. By comparative analysis of genome-wide gene expression in these conditions, we found that the mechanism of high production of rifamycin SV induced by nitrate could be elucidated.
Project description:Here we report the effect of two comparative transcriptomics experiments effect on EDDS producing biosynthetic gene cluster. The goals of this study are to compare RNA sequencing derived transcriptomes of Amycolatopsis japonica at 24 hours in zinc treated and control culture conditions in combination with control and zur regulator deleted strains, in order to target other genes for the overexpression of EDDS cluster.
