Dynamics of 5-Hydroxymethylcytosine and Chromatin Marks in Mammalian Neurogenesis

Maria A. Hahn; Runxiang Qiu; Xiwei Wu; Arthur X. Li; Heying Zhang; Jun Wang; Jonathan Jui; Seung-Gi Jin; Yong Jiang; Gerd P. Pfeifer; Qiang Lu

doi:10.1016/j.celrep.2013.01.011

Cell Reports (Feb 2013)

Dynamics of 5-Hydroxymethylcytosine and Chromatin Marks in Mammalian Neurogenesis

Maria A. Hahn,
Runxiang Qiu,
Xiwei Wu,
Arthur X. Li,
Heying Zhang,
Jun Wang,
Jonathan Jui,
Seung-Gi Jin,
Yong Jiang,
Gerd P. Pfeifer,
Qiang Lu

Affiliations

Maria A. Hahn: Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
Runxiang Qiu: Department of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
Xiwei Wu: Department of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
Arthur X. Li: Department of Information Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
Heying Zhang: Department of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
Jun Wang: Department of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
Jonathan Jui: Department of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
Seung-Gi Jin: Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
Yong Jiang: Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
Gerd P. Pfeifer: Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA
Qiang Lu: Department of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA

DOI: https://doi.org/10.1016/j.celrep.2013.01.011
Journal volume & issue: Vol. 3, no. 2
pp. 291 – 300

Abstract

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DNA methylation in mammals is highly dynamic during germ cell and preimplantation development but is relatively static during the development of somatic tissues. 5-hydroxymethylcytosine (5hmC), created by oxidation of 5-methylcytosine (5mC) by Tet proteins and most abundant in the brain, is thought to be an intermediary toward 5mC demethylation. We investigated patterns of 5mC and 5hmC during neurogenesis in the embryonic mouse brain. 5hmC levels increase during neuronal differentiation. In neuronal cells, 5hmC is not enriched at enhancers but associates preferentially with gene bodies of activated neuronal function-related genes. Within these genes, gain of 5hmC is often accompanied by loss of H3K27me3. Enrichment of 5hmC is not associated with substantial DNA demethylation, suggesting that 5hmC is a stable epigenetic mark. Functional perturbation of the H3K27 methyltransferase Ezh2 or of Tet2 and Tet3 leads to defects in neuronal differentiation, suggesting that formation of 5hmC and loss of H3K27me3 cooperate to promote brain development.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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