Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Feb 2:2021:8817581.
doi: 10.1155/2021/8817581. eCollection 2021.

Chromatin Regulation in Development: Current Understanding and Approaches

Zi Hao Zheng  1   2 , Tsz Wing Sam  1   2 , YingYing Zeng  1   3 , Justin Jang Hann Chu  4   5   6   7 , Yuin-Han Loh  1   2   7   8
Affiliations
Review

Chromatin Regulation in Development: Current Understanding and Approaches

Zi Hao Zheng et al. Stem Cells Int. .

Abstract

The regulation of mammalian stem cell fate during differentiation is complex and can be delineated across many levels. At the chromatin level, the replacement of histone variants by chromatin-modifying proteins, enrichment of specific active and repressive histone modifications, long-range gene interactions, and topological changes all play crucial roles in the determination of cell fate. These processes control regulatory elements of critical transcriptional factors, thereby establishing the networks unique to different cell fates and initiate waves of distinctive transcription events. Due to the technical challenges posed by previous methods, it was difficult to decipher the mechanism of cell fate determination at early embryogenesis through chromatin regulation. Recently, single-cell approaches have revolutionised the field of developmental biology, allowing unprecedented insights into chromatin structure and interactions in early lineage segregation events during differentiation. Here, we review the recent technological advancements and how they have furthered our understanding of chromatin regulation during early differentiation events.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interests. The data used for analysis were sourced from Gene Expression Omnibus. Search was conducted for human and mouse genomic data with relevant key terms such as “ATAC,” “ChIP-seq,” “ESC,” and “TSC.” Literature search was conducted using PubMed, Google Scholar, Nature, Cell Press, Science Magazine with a combination of keywords such as “Single-Cell,” “Embryogenesis,” “Stem cell differentiation,” “Trophoblast differentiation,” “Histone variant,” “Transposable element,” “Totipotency,” “Transdifferentiation,” and “Histone modifier.” The search results were considered based on novelty, potential impact, and possible applications.

Figures

Figure 1
Figure 1
Summary of the comparison of different single-cell and low-input techniques to assess chromatin structure [–, –, , , –38]. Created with http://BioRender.com/.
Figure 2
Figure 2
Summary of the comparison in deriving mouse and human ESCs and TSCs from mouse and human ESCs [, , , , , –, , , –85]. Created with http://BioRender.com/.
Figure 3
Figure 3
Transposable elements are marked by epigenetic signatures. (a) Dot-plot of the enrichment of transposable elements families in 8 chromatin marks and 11 bound factors in mouse TSCs. The size of the circle represents corrected enrichment P values. The colour indicates the enrichment score which was computed with a combination of the binomial test and hypergeometric test [89]. (b) Dot-plot of the enrichment of transposable elements families in open chromatin regions defined by ATAC-seq peaks in human eight-stage blastocysts, naïve ESCs, primed ESCs, blastocyst-derived TSCs, H9-derived TSCs, and AN1 iPSC-derived TSCs. The size of the circle represents corrected enrichment P values. The colour indicates the enrichment score which was computed with a combination of the binomial test and hypergeometric test [89].
See this image and copyright information in PMC

References

    1. Kantidze O. L., Razin S. V. Weak interactions in higher-order chromatin organization. Nucleic Acids Research. 2020;48(9):4614–4626. doi: 10.1093/nar/gkaa261. - DOI - PMC - PubMed
    1. Macfarlan T. S., Gifford W. D., Driscoll S., et al. Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature. 2012;487(7405):57–63. doi: 10.1038/nature11244. - DOI - PMC - PubMed
    1. Yang Y., Liu B., Xu J., et al. Derivation of pluripotent stem cells with in vivo embryonic and extraembryonic potency. Cell. 2017;169(2):243–257.e25. doi: 10.1016/j.cell.2017.02.005. - DOI - PMC - PubMed
    1. Yang J., Ryan D. J., Wang W., et al. Establishment of mouse expanded potential stem cells. Nature. 2017;550(7676):393–397. doi: 10.1038/nature24052. - DOI - PMC - PubMed
    1. Abad M., Mosteiro L., Pantoja C., et al. Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature. 2013;502(7471):340–345. doi: 10.1038/nature12586. - DOI - PubMed

LinkOut - more resources