Abstract

Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven translocation (TET) enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews (Tupaia belangeri chinensis). The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.

Highlights

  • Epigenetic systems emphasize the heritable changes in gene expression that do not involve coding sequence modifications, e.g., DNA methylation, histone modification and chromatin remodeling, and non-coding RNA regulation

  • Spatiotemporal-biased increase of 5hmC in tree shrew brains during postnatal development To address if postnatal brain development could be attributed to active DNA demethylation, we examined the 5hmC levels in the prefrontal cortex (PFC), parietal cortex (PC), occipital cortex (OC), hippocampus (HP), and cerebellum (CB) of P10, 3-month, and 1-year-old tree shrew brains using immunohistochemistry

  • Age-related decrease of 5hmC in tree shrew brains during aging 5hmC-mediated epigenetic regulation plays an important role in brain development, whether it is involved in brain aging remains unclear

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Summary

Introduction

Epigenetic systems emphasize the heritable changes in gene expression that do not involve coding sequence modifications, e.g., DNA methylation, histone modification and chromatin remodeling, and non-coding RNA regulation. These types of changes are proposed to be responsible for controlling the expression and function of genes and have emerged as important mediators of development and aging (Abel & Zukin, 2008; Agis-Balboa et al, 2013; Alagiakrishnan et al, 1 2012; Bakulski et al, 2012; Barbash & Soreq, 2012; Bihaqi et al, 2012; Coppieters & Dragunow, 2011; Deaton & Bird, 2011). Other mental retardation disorders are linked to the disruption of genes involved in epigenetic mechanisms, e.g., alpha thalassemia/mental retardation X-

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