Chromatin remodeling and gene regulation in simple eukaryotes
Co-workers: Mr Nagarajan Ahamarshan; Dr Michael Youdell; Dr Ivan Boubriak; Mrs Anitha Nair; Mr Pieter Swanepoel; Ms Ana Serra-Barros; Mr Jon Ayling; Ms Françoise Howe; Ms Tania Nguyen
Controlled access to the information stored in our DNA genomes is mediated in part by our epigenome; the layer of information that influences events on the DNA without altering the DNA sequence. Epigenetic control of gene expression occurs in three main ways; by non-coding RNAs, by methylation of CG dinucleotides in DNA and through various reversible covalent modifications to histone proteins. Defects in epigenetic control processes make a significant contribution to age-related diseases, particularly cancer, and a global effort is underway to decipher the epigenetic code and to understand how it influences gene expression.
My group uses the budding yeast Saccharomyces cerevisiae as a model organism in which to study how non-coding RNAs, higher order structures in chromatin (determined using predictive pattern recognition algorithms) and histone modifications influence the response to changes in nutrient availability. Caloric restriction is known to increase lifespan in a wide range of organisms including yeast and may ameliorate the effects of age-related diseases but the mechanism involved are poorly understood. Yeast offers a powerful tool for dissecting the pathways that allow cells to switch from active growth into a long-lived quiescent state. We use predictive pattern recognition algorithms, 3C analysis and most standard wet techniques including chromatin immunoprecipitation. Drug screens for modulators of longevity are being conducted in collaboration with Chronos Therapeutics.
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- Morillon, A., et al., Regulation of elongating RNA polymerase II by forkhead transcription factors in yeast. Science, 2003. 300(5618): p. 492-5
- Pinskaya, M., et al., Nucleosome remodeling and transcriptional repression are distinct functions of Isw1 in Saccharomyces cerevisiae. Mol Cell Biol, 2009. 29(9): p. 2419-30
- Mellor, J., Linking the cell cycle to histone modifications: Dot1, G1/S, and cycling K79me2. Mol Cell, 2009. 35(6): p. 729-30
- Youdell, M.L., et al., Roles for Ctk1 and Spt6 in regulating the different methylation states of histone H3 lysine 36. Mol Cell Biol, 2008. 28(16): p. 4915-26
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