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Stability and flexibility of epigenetic gene regulation in mammalian development

Nature volume 447, pages 425–432 (2007)Cite this article

Abstract

During development, cells start in a pluripotent state, from which they can differentiate into many cell types, and progressively develop a narrower potential. Their gene-expression programmes become more defined, restricted and, potentially, 'locked in'. Pluripotent stem cells express genes that encode a set of core transcription factors, while genes that are required later in development are repressed by histone marks, which confer short-term, and therefore flexible, epigenetic silencing. By contrast, the methylation of DNA confers long-term epigenetic silencing of particular sequences — transposons, imprinted genes and pluripotency-associated genes — in somatic cells. Long-term silencing can be reprogrammed by demethylation of DNA, and this process might involve DNA repair. It is not known whether any of the epigenetic marks has a primary role in determining cell and lineage commitment during development.

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Figure 1: Epigenetic gene regulation during mammalian development.
Figure 2: Epigenetic regulation of pluripotency-associated genes and developmental genes during the differentiation of somatic cells and germ cells.
Figure 3: Developmental regulation of imprinting and X-chromosome inactivation.
Figure 4: Reprogramming of epigenetic marks in the germ line and the early embryo.

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Acknowledgements

I thank all my colleagues, past and present, for their contributions to the work and ideas described in this paper, especially W. Dean, F. Santos, A. Lewis, and G. Smits. Funding from the Biotechnology and Biological Sciences Research Council, the Medical Research Council, the European Union Epigenome Network of Excellence, CellCentric and the Department of Trade & Industry is gratefully acknowledged.

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  1. Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge, CB22 3AT, UK

    Wolf Reik

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The author is a consultant to CellCentric (Cambridge, UK), a small company that takes epigenetic approaches to medicine.

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Correspondence should be addressed to the author (wolf.reik@bbsrc.ac.uk).

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Reik, W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447, 425–432 (2007). https://doi.org/10.1038/nature05918

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