RIKEN Center for Biosystems Dynamics Research Laboratory for Developmental Epigenetics

Team Leader: Ichiro Hiratani (Ph.D.)

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Research Summary

Understanding the 3D organization of the genomic DNA, which is the source of heredity, is essential for life science because it would lead to a fundamental understanding of various genome functions. However, many difficult questions remain unresolved. We are tackling these challenging questions by focusing on DNA replication regulation, which reflects the 3D genome structure. In particular, we aim to understand the regulation of the 3D genome organization during development, differentiation, and disease progression by combining advanced technologies such as scRepli-seq, our homemade genome-wide single-cell DNA replication sequencing technology, and Hi-C, a genome-wide methodology for analyzing the 3D genome architecture.

Main Research Fields

Biology

Related Research Fields

Biological Sciences

Keywords

3D genome organization
Epigenetics
DNA replication timing
Embryonic stem cell differentiation
Single-cell genome-wide sequencing technology

Selected Publications

1. Miura H. and Hiratani I.:
"Cell cycle dynamics and developmental dynamics of the 3D genome: toward linking the two timescales."
Curr Opin Genet Dev 73:101898 (2022)
2. Hada M., Miura H., Tanigawa A., et al.:
"Highly rigid H3.1/H3.2–H3K9me3 domains set a barrier for cell fate reprogramming in trophoblast stem cells."
Genes Dev 36:84-102 (2022)
3. Connolly C., Takahashi S., Miura H., et al.:
"SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication."
J Cell Sci 135:jcs258991 (2022)
4. Poonperm R. and Hiratani I.:
"Formation of a multi-layered 3-dimensional structure of the heterochromatin compartment during early mammalian development."
Dev Growth Differ 63:5-17 (2021)
5. Miura H., Takahashi S., Shibata T., et al.:
"Mapping replication timing domains genome wide in single mammalian cells with single-cell DNA replication sequencing."
Nat Protoc 15:4058-4100 (2020)
6. Kadota M., Nishimura O., Miura H., et al.:
"Multifaceted Hi-C benchmarking: what makes a difference in chromosome-scale genome scaffolding?"
Gigascience 9:giz158 (2020)
7. Abdalla M.O.A., Yamamoto T., Maehara K., et al.:
"The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis."
Nat Commun 10:3778 (2019)
8. Miura H., Takahashi S., Poonperm R., et al.:
"Single-cell DNA replication profiling identifies spatiotemporal developmental dynamics of chromosome organization."
Nat Genet 51:1356-1368 (2019)
9. Hiratani I. and Takahashi S.:
"DNA replication timing enters the single-cell era."
Genes 10:221 (2019)
10. Takahashi S., Miura H., Shibata T., et al.:
"Genome-wide stability of the DNA replication program in single mammalian cells."
Nat Genet 51:529-540 (2019)