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Our research on heterochromatin

An enormous amount of genetic information is stored in DNA. In humans, the total length of DNA from a single cell is approximately 2 meters, which then must fit into a 10-micron nucleus. Therefore, DNA must be precisely folded so that genetic functions such as transcription and replication can be performed, although the folds themselves play an important role in gene regulation. The foundation for DNA folding is the chromatin structure. A variety of folded structures can be assumed when DNA wraps around proteins known as histones.

When we investigate gene expression in a variety of cells, only about 10% of the genes are expressed; the remaining 90% of genes are not expressed. The expression pattern of genes is determined during cell differentiation. Genetic information in the form of a DNA sequence remains the same in the process of differentiation. The patterns of gene expression, once determined, are stably maintained even after cell division. In this way, the mechanism of regulating a “stable” gene expression without changing the genes themselves is called “epigenetics.” Epigenetics is not only involved in cell differentiation, but also in oncogenesis and senescence. It is also important in the construction of iPS cells, a topic of recent interest, with applications to regenerative medicine. Importantly, the regulation of epigenetic gene expression is directly controlled by chromatin. Heterochromatin is not only associated with epigenetic regulation of gene expression, but is also deeply involved in the maintenance of genetic information, thus making it an important and complex chromatin structure.

An important aspect of researching biological phenomena is to select the appropriate model organism. We use the fission yeast as a model because its chromatin structure is similar to that of higher eukaryotes, although it is much simpler. In addition, mutants can be easily created in fission yeast. Various genes affecting the morphology and function of heterochromatin have been identified through the isolation and characterization of fission yeast mutant strains with abnormalities in its heterochromatin. We are aggressively analyzing several genes in relation to when, where, and how these function, including their reciprocal relationships. A variety of methods are being used to analyze its protein products, including the functional analysis, structural analysis of changes in heterochromatin structure using mutant strains, and the intracellular localization of each protein using fluorescence optics.

The concepts of epigenetics and heterochromatin are closely linked to cancer, senescence, and regenerative medicine; and have garnered attention from numerous researchers, thus making it a competitive field of research. However, it is a complex subject and research on it has just begun. With this background, we are proud of the results that we have achieved thus far. However, our goal is not just to win the race but to be one step closer to the mysteries of life, using our curiosity to endlessly conduct research.

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