The genome sequences of various organisms including humans have been determined, leading to the current post-genomic era. In the future, it is likely that the genome sequences of individuals will be determined and introduced into medical practice. For example, genomic sequence information can contribute to determining an individual’s susceptibility to many diseases, including cancer. Blood types can be identified without the need for a blood test by looking at the genomic sequence. What other significant contributions can be made to society in this post-genomic era?
One of the important challenges in the post-genome era is the elucidation of epigenetic mechanisms. This epigenetic mechanism is a collective term for molecular mechanisms that control various nuclear events, including gene transcription, through modifications of DNA and histones that bind to DNA. In other words, the epigenetic mechanism controls nuclear events without altering DNA sequence. This epigenetics research field has been developing rapidly since the 1990s.
In addition, 3D Genome Organization has been highlighted as a new research field. This new field of academic research studies the 3D structure of the genome and its biological significance. For example, when activating transcription of a human gene, the region called an enhancer interacts with the promoter region of the gene. This interaction between the enhancer and the promoter is one aspect of 3D genome organization. As this example shows, genomic structures can control gene expression without altering DNA sequence. In that sense, the research of 3D genome organization can be included in a new field that expands upon the conventional field of epigenetics.
The 3D structural Model of the fission yeast genome
Using the ELP/Hi-C genomics method, we comprehensively mapped genome-wide contacts and modeled the 3D structure of the fission yeast genome using bioinformatics algorithms (Right panel; Tanizawa et al. Nucleic Acids Research 2010). Fission yeast and human IMR90 cells were subjected to DAPI staining (left panels).
The field of 3D genome organization is an immature field of research and therefore has many unexplored research themes. For instance, in the genome architecture, structures of different sizes can be detected when viewed microscopically and macroscopically. The most microscopic being the nucleosome, and the most macroscopic being a structure called the chromosome territory. In more detail, it is thought that the whole genome architecture is composed of multiply layered structures of different sizes. However, the biological roles of these differently sized genomic structures must be elucidated by further studies. Unresolved research themes in this area include:
- What kinds of genome structures exist?
- How are genome structures of different sizes formed?
- How are genomic structures of different sizes involved in various nuclear events, including transcription?
- How are 3D genomic corruptions involved in human disease?
Our laboratory is exploring the research themes above, utilizing cutting-edge genomics based on next-generation sequencing, as well as microscopic, molecular biological, biochemical, and genetic methods. The 3D Genomic Organization research field explores the structure of genetic material that is the most fundamental for living organisms. Why don't you become absorbed in the fascinating structure of the 3D genome by engaging in genome research?
Please refer to the Research for more specific research content.
If you are interested in our research, please feel free to contact Ken-ichi Noma (Email: noma@igm.hokudai.ac.jp).