Photo of Team leder, Ichiro Hiratani 2023

Team Director
Ichiro Hiratani Ph.D.

Laboratory for Developmental Epigenetics

Location Kobe / Developmental Biology Buildings

E-mailichiro.hiratani[at]riken.jp

Please replace [at] with @.

Unraveling the design principles of the genome through studies of the spatiotemporal dynamics of the 3D genome organization

Genomic DNA, which is the source of heredity in all living organisms, is highly compacted in three dimensions (3D) in the cell nucleus. Understanding the regulatory principles of the 3D genome organization is extremely important for life science in general because it would lead to a fundamental understanding of various genome functions such as gene expression. How is the 3D genome organization established and maintained in a cell-type specific manner in various cell types that constitute an organism? How does the 3D genome organization change when cells change their character during development, growth, and differentiation? To answer these questions, our research centers around the regulation of DNA replication, which is known to reflect the 3D genome organization. In particular, we utilize our homemade scRepli-seq method, a single-cell genome-wide DNA replication sequencing technology, and combine it with Hi-C, a genome-wide method to analyze the 3D genome organization. By using a variety of materials from early mouse embryos to cultured cells, we are tackling the aforementioned problems at the single-cell level.

Single-cell genome-wide DNA replication sequencing (scRepli-seq) data

Research Theme

Developmental dynamics of the 3D genome organization and DNA replication
Regulatory mechanisms of 3D genome organization
Development of single-cell genome-wide technologies for studies of the 3D genome organization

Selected Publications

Miura H, Hiratani I.
Cell cycle dynamics and developmental dynamics of the 3D genome: toward linking the two timescales.
Current Opinion in Genetics & Development 73, 101898 (2022) doi: 10.1016/j.gde.2021.101898

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 & Development 36, 84-102 (2022) doi: 10.1101/gad.348782.121

Connolly C, Takahashi S, Miura H, et al.
SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication.
Journal of Cell Science 135(2), jcs258991 (2022) doi: 10.1242/jcs.258991

Poonperm R, Hiratani I.
Formation of a multi-layered 3-dimensional structure of the heterochromatin compartment during early mammalian development.
Development, Growth & Differentiation 63(1), 5-17 (2021) doi: 10.1111/dgd.12709

Miura H, Takahashi S, Shibata T, et al.
Mapping replication timing domains genome wide in single mammalian cells with single-cell DNA replication sequencing.
Nature Protocols 15(12), 4058-4100 (2020) doi: 10.1038/s41596-020-0378-5

Kadota M, Nishimura O, Miura H, et al.
Multifaceted Hi-C benchmarking: what makes a difference in chromosome-scale genome scaffolding?
GigaScience 9(1), giz158 (2020) doi: 10.1093/gigascience/giz158

Abdalla MOA, Yamamoto T, Maehara K, et al.
The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis.
Nature Communications 10, 3778 (2019) doi: 10.1038/s41467-019-11378-4

Miura H, Takahashi S, Poonperm R, et al.
Single-cell DNA replication profiling identifies spatiotemporal developmental dynamics of chromosome organization.
Nature Genetics 51(9), 1356-1368 (2019) doi: 10.1038/s41588-019-0474-z

Hiratani I, Takahashi S.
DNA Replication Timing Enters the Single-Cell Era.
Genes 10(3), 221 (2019) doi: 10.3390/genes10030221

Takahashi S, Miura H, Shibata T, et al.
Genome-wide stability of the DNA replication program in single mammalian cells.
Nature Genetics 51(3), 529-540 (2019) doi: 10.1038/s41588-019-0347-5