Research

Cells within an individual of a multicellular organism have essentially the same DNA sequence.In order for a cell to express a unique feature, it is necessary to utilize cell-type specific genes, and "epigenetics" makes this possible. Epigenetics is a mechanism that specifies the active or silent state of genes by applying chemical modifications to DNA and histone proteins without changing the DNA sequence (Fig. 1).

The core of its regulation is conserved among many eukaryotes and plays an important role in a variety of biological processes, including reproduction, development, and environmental responses.

The genomic DNA of many organisms contains not only genes necessary for vital functions, but also large amounts of potentially harmful elements such as transposable elements and viruses.Therefore, organisms are to properly identify these genes/elements and regulate their expression by applying appropriate epigenetic modifications to each of them. Abnormalities or breakdowns in this mechanism can induce developmental abnormalities and diseases such as cancer.Despite such importance, how does an organism distinguish between genes and harmful elements in its genome?When and in which cells? What happens when a new harmful elements is introduced from the outside? Many mysteries still remain unsolved.

Our laboratory is vigorously pursuing both basic and applied research on epigenetics (Figure 2),the fundamental mechanism that controls many biological events, using plants and fission yeast as experimental materials (Figure 3).In particular, we are trying to elucidate how organisms appropriately regulate genes and harmful elements through epigenetic modifications, how such modifications are inherited from one generation to the next, and how environmental changes affect epigenomic patterns. In addition, based on such results of basic researches, we are challenging the development of artificial epigenome editing technology.We aim to apply the resulting new technologies not only to model organisms but also to crops and animal cells, thereby contributing to the achievement of the SDGs and the development of medical technologies.

Project 1 How plants distinguish between genes and transposons

Organisms find transposons and other harmful sequences lurking in their genomic DNA and use epigenetic mechanisms to suppress their expression. However, this fundamental question of how exactly the mechanism works has remained an unsolved mystery. We aim to unravel its secrets by focusing on the construction of epigenetic modifications in plants.

Project 2 Mystery of DNA methylation in genes

Intragenic DNA methylation is an important DNA methylation that occurs inside a gene, i.e., within the coding region. Although DNA methylation is usually thought to be involved in gene repression, intragenic methylation is not responsible for gene repression. Although intragenic DNA methylation has been identified in many eukaryotes, its underlying function remains a mystery. We are trying to elucidate its function.

Project 3 The relationship between the environment and epigenetics

Epigenetics plays an important role in enabling organisms to respond to and adapt to their environment; epigenetic mechanisms such as DNA methylation and histone modifications are deeply involved in the process by which organisms alter their gene function and metabolism in response to environmental changes. Our research will reveal how environmental changes affect the epigenome and genome dynamics.

Project 4 Development of Artificial Epigenome Editing Technology

Epigenome editing is a technology that introduces or modifies epigenetic modifications into specific regions to alter gene expression or function. While conventional gene editing technologies (e.g., CRISPR-Cas9) alter the DNA base sequence itself, epigenome editing manipulates epigenetic modifications such as DNA methylation and histone modifications. This makes it possible to activate or repress genes and alter cell function and behavior. We are vigorously developing epigenome editing technology by extending the results of our basic research on the mechanism of epigenome construction in plants, with the aim of applying the technology to functional modification of plants and treatment of human diseases.

TO Laboratory, Tokyo Institute of Technology