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Single-cell DNA replication profiling identifies spatiotemporal developmental dynamics of chromosome organization [BrdU-IP Repli-chip]


ABSTRACT: In mammals, chromosomes are partitioned into megabase-sized topologically associating domains (TADs). TADs can be in either A (active) or B (inactive) subnuclear compartments, which correspond to early (E) and late (L) replicating timing (RT) domains, respectively. Here, we show that RT changes are tightly correlated with A/B compartment changes during mouse embryonic stem cell (mESC) differentiation. A/B compartments changed mostly by a “boundary shift,” frequently causing compartment switching of single TADs, which coincided with or preceded RT changes. Upon differentiation, mESCs acquired an A/B compartment organization that closely resembled EpiSCs (epiblast-derived stem cells), suggesting that accumulation of compartment boundary repositioning eventually led to naïve-to-primed pluripotency transition in A/B compartment organization. We propose that large-scale reorganization of A/B compartments, which is reflected in RT domain reorganization, represents major cell fate changes. Collectively, our data provides valuable insights into the regulatory principles of 3-dimensional (3D) genome organization during early embryonic stages.

ORGANISM(S): Mus musculus

PROVIDER: GSE113984 | GEO | 2019/06/26

REPOSITORIES: GEO

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