Laboratory for Nuclear Dynamics

Member

Professor Takahisa FURUKAWA
Specially-appointed Professor Takashi NAGANO

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Research

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.

Current Research Programs

  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

References

  1. Collombet S, Ranisavljevic N, Nagano T, et al. Parental-to-embryo switch of chromosome organization in early embryogenesis. Nature. 2020, 580: 142-146.
  2. Nagano T, Lubling Y, Várnai C, et al. Cell-cycle dynamics of chromosomal organization at single-cell resolution. Nature. 2017, 547: 61-67.
  3. Nagano T, Lubling Y, Yaffe E, et al. Single-cell Hi-C for genome-wide detection of chromatin interactions that occur simultaneously in a single cell. Nat Protoc. 2015, 10: 1986-2003.
  4. Nagano T, Várnai C, Schoenfelder S, et al. Comparison of Hi-C results using in-solution versus in-nucleus ligation. Genome Biol. 2015, 16: 175.
  5. Nagano T, Lubling Y, Stevens TJ, et al. Single-cell Hi-C reveals cell-to-cell variability in chromosome structure. Nature. 2013, 502: 59-64.