Reports summarize gene therapy research from University of Montreal
2009 JUL 9 - (NewsRx.com) -- According to a study from Montreal, Canada, "Cap1p, a transcription factor of the basic region leucine zipper family, regulates the oxidative stress response (OSR) in Candida albicans. Alteration of its C-terminal cysteine-rich domain (CRD) results in Cap1p nuclear retention and transcriptional activation." "To better understand the function of Cap1p in C. albicans, we used genome-wide location profiling (chromatin immunoprecipitation-on-chip) to identify its transcriptional targets in vivo. A triple-hemagglutinin (HA(3)) epitope was introduced at the C terminus of wild-type Cap1p (Cap1p-HA(3)) or hyperactive Cap1p with an altered CRD (Cap1p-CSE-HA(3)). Location profiling using whole-genome oligonucleotide tiling microarrays identified 89 targets bound by Cap1p-HA(3) or Cap1p-CSE-HA(3) (the binding ratio was at least twofold; P<= 0.01). Strikingly, Cap1p binding was detected not only at the promoter region of its target genes but also at their 3' ends and within their open reading frames, suggesting that Cap1p may associate with the transcriptional or chromatin remodeling machinery to exert its activity. Overrepresented functional groups of the Cap1p targets (P <= 0.02) included 11 genes involved in the OSR (CAP1, GLR1, TRX1, SOD1, CAT1, and others), 13 genes involved in response to drugs (PDR16, MDR1, FLU1, YCF1, FCR1, and others), 4 genes involved in phospholipid transport (PDR16, GIT1, RTA2, and orf19.932), and 3 genes involved in the regulation of nitrogen utilization (GST3, orf19.2693, and orf19.3121), suggesting that Cap1p has other cellular functions in addition to the OSR. Bioinformatic analyses of the bound sequences suggest that Cap1p recognizes the DNA motif 5'-MTKASTMA," wrote S. Znaidi and colleagues, University of Montreal. The researchers concluded: "Finally, transcriptome analyses showed that increased expression generally accompanies Cap1p binding at its targets, indicating that Cap1p functions as a transcriptional activator." Znaidi and colleagues published the results of their research in Eukaryotic Cell (Identification of the Candida albicans Cap1p Regulon. Eukaryotic Cell, 2009;8(6):806-820). For additional information, contact M. Raymond, University of Montreal, Institute Research Immunology & Cancer, POB 6128, Station Center Ville, Montreal, PQ H3C 3J7, Canada. The publisher of the journal Eukaryotic Cell can be contacted at: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA. Keywords: Canada, Montreal, Biotechnology, Cysteine, Dietary Supplement, Gene Therapy, Nutritional Supplement, University of Montreal. This article was prepared by Gene Therapy Weekly editors from staff and other reports. Copyright 2009, Gene Therapy Weekly via NewsRx.com.
|
