Cell-wide DNA de-methylation and re-methylation of purkinje neurons in the developing cerebellum

Feng Zhou, Marisol Resendiz, Chiao Ling Lo, Yuanyuan Chen

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Global DNA de-methylation is thought to occur only during pre-implantation and gametogenesis in mammals. Scalable, cell-wide de-methylation has not been demonstrated beyond totipotent stages. Here, we observed a large scale de-methylation and subsequent re-methylation (CDR) (including 5-methylcytosine (5mC) and 5-hydroxylmethylcytosine (5hmC)) in post-mitotic cerebellar Purkinje cells (PC) through the course of normal development. Through single cell immuno-identification and cell-specific quantitative methylation assays, we demonstrate that the CDR event is an intrinsically scheduled program, occurring in nearly every PC. Meanwhile, cerebellar granule cells and basket interneurons adopt their own DNA methylation program, independent of PCs. DNA de-methylation was further demonstrated at the gene level, on genes pertinent to PC development. The PC, being one of the largest neurons in the brain, may showcase an amplified epigenetic cycle which may mediate stage transformation including cell cycle arrest, vast axonal-dendritic growth, and synaptogenesis at the onset of neuronal specificity. This discovery is a key step toward better understanding the breadth and role of DNA methylation and de-methylation during neural ontology.

Original languageEnglish (US)
Article number0162063
JournalPLoS One
Volume11
Issue number9
DOIs
StatePublished - Sep 1 2016

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Methylation
Purkinje Cells
cerebellum
DNA Methylation
methylation
Cerebellum
Neurons
neurons
DNA
cells
5-Methylcytosine
Gametogenesis
DNA methylation
Genes
Interneurons
Cell Cycle Checkpoints
Epigenomics
Mammals
interneurons
Ion implantation

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Cell-wide DNA de-methylation and re-methylation of purkinje neurons in the developing cerebellum. / Zhou, Feng; Resendiz, Marisol; Lo, Chiao Ling; Chen, Yuanyuan.

In: PLoS One, Vol. 11, No. 9, 0162063, 01.09.2016.

Research output: Contribution to journalArticle

Zhou, Feng ; Resendiz, Marisol ; Lo, Chiao Ling ; Chen, Yuanyuan. / Cell-wide DNA de-methylation and re-methylation of purkinje neurons in the developing cerebellum. In: PLoS One. 2016 ; Vol. 11, No. 9.
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