Developmental changes and sex differences in DNA methylation and demethylation in hypothalamic regions of the mouse brain.

Epigenetics : Official Journal of the DNA Methylation Society
Carla D CisternasNancy G Forger

Abstract

DNA methylation is dynamically modulated during postnatal brain development, and plays a key role in neuronal lineage commitment. This epigenetic mark has also recently been implicated in the development of neural sex differences, many of which are found in the hypothalamus. The level of DNA methylation depends on a balance between the placement of methyl marks by DNA methyltransferases (Dnmts) and their removal, which is catalyzed by ten-eleven translocation (Tet) methylcytosine dioxygenases. Here, we examined developmental changes and sex differences in the expression of Tet and Dnmt enzymes from birth to adulthood in two hypothalamic regions (the preoptic area and ventromedial nucleus) and the hippocampus of mice. We found highest expression of all Tet enzymes (Tet1, Tet2, Tet3) and Dnmts (Dnmt1, Dnmt3a, Dnmt3b) in newborns, despite the fact that global methylation and hydroxymethylation were at their lowest levels at birth. Expression of the Dnmt co-activator, Dnmt3l, followed a pattern opposite to that of the canonical Dnmts (i.e., was very low in newborns and increased with age). Tet enzyme activity was much higher at birth than at weaning in both the hypothalamus and hippocampus, mirroring developmental changes in gene e...Continue Reading

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Citations

Nov 5, 2020·Journal of Neuroendocrinology·William Kenkel
Oct 27, 2020·Frontiers in Psychiatry·Zhenghao Duan, Jie Lu
Apr 19, 2021·Biological Psychiatry·Jennifer R RainvilleGeorgia E Hodes
May 4, 2021·Reviews in the Neurosciences·Annamaria SrancikovaJan Bakos

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Methods Mentioned

BETA
dot blots
PCR
Protein Assay
Assay

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