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Epigenetic mechanisms in neurogenesis

Nature Reviews Neuroscience volume 17, pages 537–549 (2016)Cite this article

Subjects

Key Points

  • DNA methylation and DNA methyltransferases regulate neurogenesis through epigenetic control of gene expression.

  • Dynamic DNA demethylation exerts temporal control over transcription control during neurogenesis.

  • Cytosine modification derivatives and ten-eleven translocation (TET) proteins precisely coordinate neurogenesis.

  • Histone modification dynamics and their regulators can exert a broad influence over neurogenic processes both directly and indirectly.

Abstract

In the embryonic and adult brain, neural stem cells proliferate and give rise to neurons and glia through highly regulated processes. Epigenetic mechanisms — including DNA and histone modifications, as well as regulation by non-coding RNAs — have pivotal roles in different stages of neurogenesis. Aberrant epigenetic regulation also contributes to the pathogenesis of various brain disorders. Here, we review recent advances in our understanding of epigenetic regulation in neurogenesis and its dysregulation in brain disorders, including discussion of newly identified DNA cytosine modifications. We also briefly cover the emerging field of epitranscriptomics, which involves modifications of mRNAs and long non-coding RNAs.

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Figure 1: Embryonic and adult neurogenesis.
Figure 2: Major forms of epigenetic modifications.

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Acknowledgements

This work is supported by the US National Institutes of Health (NIH; NS047344 and HD086820 to H.S., NS048271, NS095348, MH110160 and MH105128 to G.L.M., NS051630, NS079625 and MH102690 to P.J.), Dr. Miriam & Sheldon G. Adelson Medical Research Foundation (to G.L.M.) and the Howard Hughes Medical Institute (to C.H.). The authors apologize to colleagues whose work was not cited owing to space limitations.

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Authors and Affiliations

  1. Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, 30322, Georgia, USA

    Bing Yao & Peng Jin

  2. Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, 21205, Maryland, USA

    Kimberly M. Christian, Guo-li Ming & Hongjun Song

  3. Department of Neurology, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, 21205, Maryland, USA

    Kimberly M. Christian, Guo-li Ming & Hongjun Song

  4. Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, 60637, Illinois, USA

    Chuan He

  5. Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, 60637, Illinois, USA

    Chuan He

  6. The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, 21205, Maryland, USA

    Guo-li Ming & Hongjun Song

  7. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, 21205, Maryland, USA

    Guo-li Ming

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PowerPoint slides

Glossary

Neural progenitor cells

(NPCs). Precursor cells of the nervous system that can produce more of themselves and differentiate into various types of neural cells.

Radial glial cells

(RGCs). Bipolar cells derived from neuroepithelial cells during embryonic stages that primarily serve as neural progenitor cells during embryonic neurogenesis.

Imprinted gene silencing

A subset of genes that display a parental-specific expression pattern. Compared with normal genes, for which both paternal and maternal alleles are expressed, imprinted genes only express one parental allele. The silencing of one imprinted allele is often mediated by epigenetic mechanisms, such as DNA methylation.

X-inactivation

Females carry two copies of the X chromosome and therefore could potentially express toxic levels (a 'double dose') of X chromosome-linked genes. To prevent this scenario, cells of an early female embryo will randomly inactivate one of the two X chromosomes for gene dosage compensation, termed X-inactivation.

TET family proteins

Ten-eleven translocation (TET) proteins serve as methylcytosine dioxygenases to convert 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in an iron-dependent manner.

DNA demethylation

An active biochemical process that removes a methyl group from cytosine; this process is catalysed by methylcytosine dioxygenases, such as ten-eleven translocation (TET) proteins.

Poised enhancers

Enhancers refer to the genomic regions that are characterized by uniquely bound transcription factors such as P300 and signature histone modifications such as histone H3 lysine 4 methylation (H3K4me1) that could potentially modulate transcription activation. Poised enhancers bear enhancer characteristics, but their functions are hampered by repressive chromatin marks such that they require additional cues to unleash their functions.

Transcriptome landscape

Global signature transcriptional patterns of different cell types. Maintaining cell type-specific gene expression is crucial for cell identity.

Interactomes

Whole sets of molecules that physically interact with given molecules. In this article, interactome specifically refers to protein–protein interactions.

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Yao, B., Christian, K., He, C. et al. Epigenetic mechanisms in neurogenesis. Nat Rev Neurosci 17, 537–549 (2016). https://doi.org/10.1038/nrn.2016.70

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