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Multicellular organisms are made up of diverse populations of many different types of cells, each of which contains an identical set of genetic information coded in its DNA. Cell differentiation and the process of development itself depend on the ability of individual cells to maintain the expression of different genes, and for their progeny to do so through multiple cycles of cell division. In recent years, we have begun to understand that the maintenance of specific patterns of gene expression does not rely on direct modifications to the DNA sequence encoding the organism's genome, but rather takes place in a heritable, “epigenetic” manner. DNA methylation, chromatin modifications and post-transcriptional gene silencing by double-stranded RNA molecules are some of the best known epigenetic phenomena. Recent studies have begun to show that these different mechanisms are closely inter-related, but a detailed understanding of these systems has yet to be developed.
Our team investigates how modifications to the structure and configuration of chromatin (complexes of nuclear DNA and proteins that provide the structural basis of chromosomes) contribute to epigenetic gene regulation and how such modifications are transmitted over generations of cellular division by studying events at the molecular scale in the model organism, fission yeast ( Saccharomyces pombe ), and in cultured mammalian cells.
Histones are a set of DNA packing proteins present in nucleosomes, the fundamental building blocks of chromatins. In our current studies, we are particularly interested in determining the specific histone modifications and the molecular recognition processes that enable modified histones to work together to construct and maintain higher-order chromatin structures. We also seek to clarify the picture of how dynamic rearrangements of chromatin structure are triggered by examining the structure and function of protein complexes that bind to and modify histones. In the future, we plan to perform more detailed analyses of the molecular mechanisms that underlie epigenetic function, as well as studies in higher organisms and epigenetic gene expression in developmental processes. |
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