Laboratory for Nuclear Dynamics

1. Developing state-of-the-art technologies to analyze the dynamic aspects of higher-order chromatin structure

2. Analyses on the dynamics and regulatory principles of higher-order chromatin structure using the cutting-edge single-cell technologies

Nearly all somatic cells within an individual human body carry identical genome. Therefore, epigenetic information (including chemical modification of DNA or chromatin proteins and higher-order (three-dimensional) chromatin structure) that modifies genome function in cell type-specific manner is essential for appropriate cell differentiation. Among such epigenetic information, higher-order chromatin structure is still enigmatic, and our research goal is to elucidate its regulation and dynamics.

To analyze higher-order chromatin structure, typical approaches are either microscopic techniques like FISH and molecular biological methods such as Hi-C. Microscopic techniques have revealed cell-to-cell variability of the structure but not on a genome-wide scale, while molecular biological methods are comprehensive throughout the genome but ignore cell-to-cell variability.

To bridge these two approaches, we pioneered to develop single-cell Hi-C in 2013 and have further improved the technique to acquire thousands of single-cell Hi-C data with reasonable genomic coverage. As a result, we have found dynamic and continuous reorganization in higher-order chromatin structure along with cell cycle progression in interphase cells.

These unprecedented dynamics open up number of further questions regarding higher-order chromatin structure, such as the relationship to DNA replication, other epigenetic information and cell differentiation. By developing state-of-the-art technologies, we aim to pursue such questions to understand how higher-order chromatin structure is regulated and involved in essential life events.