Unraveling the developmental dynamics of genome architecture through single-cell DNA replication profiling

 

Ichiro Hiratani

 

Laboratory for Developmental Epigenetics, RIKEN Center for Biosystems Dynamics Research (RIKEN BDR), Kobe, Japan

 

Hi-C technology has revolutionized genome biology, revealing that mammalian chromosomes are partitioned into megabase-sized topologically associating domains (TADs). TADs can be in either A (active) or B (inactive) nuclear compartments, which exhibit early and late DNA replication timing (RT), respectively. Several years ago, we developed a single-cell DNA replication sequencing technology, scRepli-seq, which has allowed us to monitor genome-wide RT dynamics and infer 3D genome organization dynamics in single cells. In this seminar, I will discuss our ongoing efforts to leverage scRepli-seq to understand the regulatory principles of 3D genome organization through the lens of DNA replication regulation. Topics include the 3D genome and replication dynamics during mammalian development, X-chromosome inactivation, and cell cycle, as well as our ongoing effort to understand the mechanism and significance of RT/compartment regulation.

 

References:

Takahashi S, Kyogoku H, Hayakawa T, Miura H, Oji A, Kondo Y, Takebayashi SI, Kitajima TS, Hiratani I. Embryonic genome instability upon DNA replication timing program emergence. Nature 633:686-694 (2024) https://doi.org/10.1038/s41586-024-07841-y

 

Oji A, Choubani L, Miura H, and Hiratani I. Structure and dynamics of A/B compartments and subcompartments. Curr Opin Cell Biol 90:102406 (2024) https://doi.org/10.1016/j.ceb.2024.102406

 

Poonperm R, Ichihara S, Miura H, Tanigawa A, Nagao K, Obuse C, Sado T, Hiratani I. Replication dynamics identifies the folding principles of the inactive X chromosome. Nat Struct Mol Biol 30:1224-1237 (2023)

https://doi.org/10.1038/s41594-023-01052-1

 

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)

https://doi.org/10.1016/j.gde.2021.101898

 

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)

https://doi.org/10.1111/dgd.12709

 

Miura H, Takahashi S, Shibata T, Nagao K, Obuse C, Okumura K, Ogata M, Hiratani I, Takebayashi SI. Mapping replication timing domains genome wide in single mammalian cells with single-cell DNA replication sequencing. Nat Protoc 15:4058-4100 (2020)

https://doi.org/10.1038/s41596-020-0378-5

 

Miura H, Takahashi S, Poonperm R, Tanigawa A, Takebayashi SI, Hiratani I. Single-cell DNA replication profiling identifies spatiotemporal developmental dynamics of chromosome organization. Nat Genet 51:1356-1368 (2019)

https://doi.org/10.1038/s41588-019-0474-z

 

Takahashi S, Miura H, Shibata T, Nagao K, Okumura K, Ogata M, Obuse C, Takebayashi SI, Hiratani I. Genome-wide stability of the DNA replication program in single mammalian cells. Nat Genet 51:529-540 (2019)

https://doi.org/10.1038/s41588-019-0347-5