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Age‐Dependent Levels of 5‐Methyl‐, 5‐Hydroxymethyl‐, and 5‐Formylcytosine in Human and Mouse Brain Tissues
Author(s) -
Wagner Mirko,
Steinbacher Jessica,
Kraus Theo F. J.,
Michalakis Stylianos,
Hackner Benjamin,
Pfaffeneder Toni,
Perera Arshan,
Müller Markus,
Giese Armin,
Kretzschmar Hans A.,
Carell Thomas
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201502722
Subject(s) - human brain , epigenetics , cytosine , 5 hydroxymethylcytosine , hippocampus , demethylation , biology , dna demethylation , cerebral cortex , brain tissue , dna , 5 methylcytosine , dna methylation , chemistry , microbiology and biotechnology , neuroscience , genetics , gene , gene expression
The absolute levels of 5‐hydroxymethylcytosine (hmC) and 5‐methylcytosine (mC) in human brain tissues at various ages were determined. Additionally, absolute levels of 5‐formylcytosine (fC) in adult individuals and cytosine modification levels in sorted neurons were quantified. These data were compared with age‐related fC, hmC, and mC levels in mouse brain samples. For hmC, an initial steady increase is observed, which levels off with age to a final steady‐state value of 1.2 % in human brain tissue. This level is nearly twice as high as in mouse cerebral cortex. In contrast, fC declines rapidly with age during early developmental stages, thus suggesting that while hmC is a stable epigenetic mark, fC is more likely an intermediate of active DNA demethylation during early brain development. The trends in global cytosine modification dynamics during the lifespan of an organism are conserved between humans and mice and show similar patterns in different organs.