Negative evidence for a functional role of neuronal DNMT3a in persistent pain

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Traditionally, neuroscience has had to rely on mixed tissue analysis to examine
transcriptional and epigenetic changes in the context of nervous system function or
pathology. However, particularly when studying chronic pain conditions, this approach
can be flawed, since it neglects to take into account the shifting contribution of different
cell types across experimental conditions. Here, we demonstrate this using the example
of DNA methyltransferases (DNMTs) – a group of epigenetic modifiers consisting of
Dnmt1, Dnmt3a, and Dnmt3b in mammalian cells. We used sensory neuron-specific
knockout mice for Dnmt3a/3b as well as pharmacological blockade of Dnmt1 to study
their role in nociception. In contrast to previous analyses on whole tissue, we find that
Dnmt3a and 3b protein is not expressed in adult DRG neurons, that none of the DNA
methyltransferases are regulated with injury and that interfering with their function has no
effect on nociception. Our results therefore currently do not support a role for neuronal
DNA methyltransferases in pain processing in adult animals.
Original languageEnglish
Article number332
JournalFrontiers in Molecular Neuroscience
Publication statusPublished - 12 Sept 2018


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