DNA methylation: an epigenetic watermark of former cocaine self-administration

Baker‐Andresen, Danay

doi:10.14264/uql.2015.870

Cited by 1 publication

(1 citation statement)

References 238 publications

(306 reference statements)

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“…Experiential learning induces active DNA methylation at genes that have been identified to be necessary for long-term memory formation in circuits that encode spatial, associative, and reward memories (Day et al, 2013;Duke et al, 2017;Guo et al, 2011). The changes to the DNA methylome induced in neural tissue after learning are dynamically regulated (Baker-Andresen et al, 2013;Lister and Mukamel, 2015), and 5mC can be oxidatively converted to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) enzymes and removed through base excision repair, in effect causing the erasure of the DNA methylation mark (Pastor et al, 2013;Rasmussen and Helin, 2016;Tahiliani et al, 2009). Such dynamism paired with the essential role that DNA methylation plays in learning and memory suggests that active DNA de-methylation, mediated by the TET enzymes, may be a target for therapeutic intervention to affect memory function (Kennedy and Sweatt, 2016).…”

Section: Introductionmentioning

confidence: 99%

Tet2negatively regulates memory fidelity

Zengeler

Gettens

Smith

et al. 2019

Preprint

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Despite being fully differentiated, DNA methylation is dynamically regulated in post-mitotic glutamatergic neurons in the CA1 of the hippocampus through competing active DNA methylation and de-methylation, a process that regulates neuronal plasticity. Active DNA methylation after learning is necessary for long-term memory formation, and active DNA de-methylation by the TET enzymes has been implicated as a counter-regulator of that biochemical process. We demonstrate that Tet2 functions in the CA1 as a negative regulator of long-term memory, whereby its knockdown across the CA1 or haploinsufficiency in glutamatergic neurons enhances the fidelity of hippocampal-dependent spatial and associative memory. Loci of altered DNA methylation were then determined using whole genome bisulfite sequencing from glutamatergic Tet2 haploinsufficient CA1 tissue, which revealed hypermethylation in the promoters of genes known to be transcriptionally regulated after experiential learning. This study demonstrates a link between Tet2 activity at genes important for memory formation in CA1 glutamatergic neurons and memory fidelity.

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