STRUCTURE STUDIES OF TRANSCRIPTIONAL SILENCING

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Transcriptional silencing is an epigenetic mechanism for control of gene expression. Genes located in certain regions of the eukaryotic chromosomes are permanently repressed. This heritable transcriptionally silent state is caused by altered chromatin structure that can be propagated from one generation to the next. Gene silencing has been observed in organisms ranging from yeast to human. Examples of silencing include mating-type loci in fission and budding yeasts, position effect variegation in Drosophila, and X-chromosome inactivation in mammals. In Saccharomyces cerevisiae, several protein complexes are known to be critical for establishing and maintaining transcriptional silencing at several genomic loci. They include the Silent Information Regulator proteins, Sir1p, Sir2p, Sir3p and Sir4p, and several sequence-specific DNA binding proteins, the Origin Recognition Complex (ORC), Rap1p and Abf1p. The structural basis of transcriptional silencing is still poorly understood. We will study the structure and function of the SIR proteins and ORC using X-ray crystallography as our principal method. The result of this study may facilitate an understanding of epigenetic inheritance, DNA repair and aging.