UMMS Affiliation

Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



Amino Acids, Peptides, and Proteins | Biochemistry | Cell and Developmental Biology | Cells | Cellular and Molecular Physiology | Embryonic Structures | Genetic Phenomena | Molecular Biology | Structural Biology


The temporal order of DNA replication is regulated during development and is highly correlated with gene expression, histone modifications and 3D genome architecture. We tracked changes in replication timing, gene expression, and chromatin conformation capture (Hi-C) A/B compartments over the first two cell cycles during differentiation of human embryonic stem cells to definitive endoderm. Remarkably, transcriptional programs were irreversibly reprogrammed within the first cell cycle and were largely but not universally coordinated with replication timing changes. Moreover, changes in A/B compartment and several histone modifications that normally correlate strongly with replication timing showed weak correlation during the early cell cycles of differentiation but showed increased alignment in later differentiation stages and in terminally differentiated cell lines. Thus, epigenetic cell fate transitions during early differentiation can occur despite dynamic and discordant changes in otherwise highly correlated genomic properties.


chromatin 3D architecture, chromatin 3D organization, chromatin structure, differentiation, gene expression, lineage commitment, replication timing

Rights and Permissions

Copyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (

DOI of Published Version



Stem Cell Reports. 2019 Jul 9;13(1):193-206. doi: 10.1016/j.stemcr.2019.05.021. Epub 2019 Jun 20. Link to article on publisher's site

Journal/Book/Conference Title

Stem cell reports


Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.