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Now accepting applications for a postdoctoral position.
Our laboratory is interested in epigenetic control of genome organization, which allows for heritable changes in gene function that are not due to changes in the DNA sequence. In eukaryotic cells, genomic DNA is folded with histone and non-histone proteins in the form of chromatin. The building block of chromatin is the nucleosome, which contains 146 bp of DNA wrapped around an octamer of histones. Factors involved in covalent modifications of histones, together with chromatin-remodeling activities and DNA modifications, are components of intricate epigenetic mechanisms that help organize genomes into discrete domains that plays important regulatory roles in almost every aspect of DNA metabolism. These epigenetic mechanisms gradually restrict the developmental potential of stem cells during differentiation and also constitute “memories” of gene activity that ensure faithful inheritance of cell identity. Defects in epigenetic regulation have been extensively demonstrated to have causal roles in numerous developmental disorders and cancers.
Recently, extensive efforts have been undertaken to identify new epigenetic histone modifications and the enzymes that catalyze these modifications. However, how histone-modifying activities are targeted to specific locations and how their activities are regulated is poorly understood. In addition, apart from a few well-known examples, how the cellular machinery interprets these modifications to achieve diverse epigenetic states is not clear. Using the fission yeast Schizosaccharomyces pombe as a model system, our laboratory combines biochemical, genetic, cytological, genomics and bioinformatics approaches to study these questions that provide molecular basis of epigenetic regulation. Advantages of fission yeast include highly conserved histone modifications, simple genome organization, a completely sequenced genome, and amenability to genetic and biochemical manipulations. All of these offer unprecedented opportunities for assessing the role of histone modification in the epigenetic regulation of the genome, which is essential to our understanding of stem cell and cancer biology.
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