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 18:9:645335.
doi: 10.3389/fcell.2021.645335. eCollection 2021.

TET Enzymes and 5-Hydroxymethylcytosine in Neural Progenitor Cell Biology and Neurodevelopment

Ian C MacArthur  1   2   3 , Meelad M Dawlaty  1   2   3
Affiliations
Review

TET Enzymes and 5-Hydroxymethylcytosine in Neural Progenitor Cell Biology and Neurodevelopment

Ian C MacArthur et al. Front Cell Dev Biol. .

Abstract

Studies of tissue-specific epigenomes have revealed 5-hydroxymethylcytosine (5hmC) to be a highly enriched and dynamic DNA modification in the metazoan nervous system, inspiring interest in the function of this epigenetic mark in neurodevelopment and brain function. 5hmC is generated by oxidation of 5-methylcytosine (5mC), a process catalyzed by the ten-eleven translocation (TET) enzymes. 5hmC serves not only as an intermediate in DNA demethylation but also as a stable epigenetic mark. Here, we review the known functions of 5hmC and TET enzymes in neural progenitor cell biology and embryonic and postnatal neurogenesis. We also discuss how TET enzymes and 5hmC regulate neuronal activity and brain function and highlight their implications in human neurodevelopmental and neurodegenerative disorders. Finally, we present outstanding questions in the field and envision new research directions into the roles of 5hmC and TET enzymes in neurodevelopment.

Keywords: 5-hydroxymethylcytosine; TET enzymes; epigenetics; neural progenitor cells; neurodevelopmental disorders; neurogenesis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Overview of the multifaceted roles of TET enzymes and 5hmC in the epigenetic regulation of mamalian neurobiology.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Antunes C., Da Silva J. D., Guerra-Gomes S., Alves N. D. F., Ferreira F., Loureiro-Campos E., et al. (2020). Tet3 ablation in adult brain neurons increases anxiety-like behavior and regulates cognitive function in mice. Mol. Psychiatry. 10.1038/s41380-020-0695-7 [Epub ahead of print]. - DOI - PubMed
    1. Bachman M., Uribe-Lewis S., Yang X., Williams M., Murrell A., Balasubramanian S. (2014). 5-Hydroxymethylcytosine is a predominantly stable DNA modification. Nat. Chem. 6 1049–1055. 10.1038/nchem.2064 - DOI - PMC - PubMed
    1. Baumann V., Wiesbeck M., Breunig C. T., Braun J. M., Koferle A., Ninkovic J., et al. (2019). Targeted removal of epigenetic barriers during transcriptional reprogramming. Nat. Commun. 10:2119. 10.1038/s41467-019-10146-8 - DOI - PMC - PubMed
    1. Beck D. B., Petracovici A., He C., Moore H. W., Louie R. J., Ansar M., et al. (2020). Delineation of a human mendelian disorder of the DNA demethylation machinery: TET3 deficiency. Am. J. Hum. Genet. 106 234–245. 10.1016/j.ajhg.2019.12.007 - DOI - PMC - PubMed
    1. Bogdanovic O., Smits A. H., de la Calle Mustienes E., Tena J. J., Ford E., Williams R. (2016). Active DNA demethylation at enhancers during the vertebrate phylotypic period. Nat. Genet. 48 417–426. 10.1038/ng.3522 - DOI - PMC - PubMed

LinkOut - more resources