Seminar “Single-cell DNA replication timing profiling and the 3D genome organization dynamics”

Plant Epigenetics Unit (Saze unit) would like to invite you to a seminar by Dr. Ichiro Hiratani.

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Date: Thursday, July 20^th
Time: 15:00 - 16:00
Venue: C016, Level C, Lab1
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Speaker: Dr. Ichiro Hiratani, Team Leader, Laboratory for Developmental Epigenetics, RIKEN CDB, Kobe, Japan

Title: “Single-cell DNA replication timing profiling and the 3D genome organization dynamics”

Abstract:
Understanding the 3D genome organization and its dynamics is a central challenge in chromosome biology. The best contemporary method to analyze the 3D genome organization is the high-resolution chromosome conformation capture assay, Hi-C. However, obtaining Hi-C data from single cells at high resolution is technically and theoretically challenging. Meanwhile, we recently found that replication timing (RT) profiles correlate well with Hi-C data and RT changes dynamically correlate with changes in A (open) and B (closed) subnuclear compartments defined by Hi-C. Importantly, single-cell RT profiling is theoretically feasible, which would allow us to predict A/B compartment organization in single cells at high resolution. Here, we report the first single-cell RT profiling method by next generation sequencing, which is based on measuring copy number changes upon DNA replication during S-phase. Our results reveal that Mb-sized RT domains exist at the single-cell level and that the degree of cell-to-cell heterogeneity is relatively low, which suggests that A/B compartment organization is conserved from cell to cell. In addition, our F1 hybrid mouse embryonic stem cells (mESCs) allowed us to obtain haplotype-resolved RT data. In particular, a single late-replicating inactive X chromosome (Xi) was evident in differentiated female mESCs. Thus, our novel RT profiling method opens the door to tracking the dynamics of subnuclear compartments and the Xi structure during differentiation at the single-cell level.

We look forward to seeing many of you at the seminar.

Sincerely,
Yoko Fujitomi
Plant Epigenetics Unit (Saze unit)