Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation

Abstract

5-hydroxymethylcytosine (5-hmC) is a novel DNA modification that is highly enriched in the adult brain and dynamically regulated by neural activity. 5-hmC accumulates across the lifespan; however, the functional relevance of this change in 5-hmC and whether it is necessary for behavioral adaptation have not been fully elucidated. Moreover, although the ten-eleven translocation (Tet) family of enzymes is known to be essential for converting methylated DNA to 5-hmC, the role of individual Tet proteins in the adult cortex remains unclear. Using 5-hmC capture together with high-throughput DNA sequencing on individual mice, we show that fear extinction, an important form of reversal learning, leads to a dramatic genome-wide redistribution of 5-hmC within the infralimbic prefrontal cortex. Moreover, extinction learning-induced Tet3-mediated accumulation of 5-hmC is associated with the establishment of epigenetic states that promote gene expression and rapid behavioral adaptation.

Publication DOI: https://doi.org/10.1073/pnas.1318906111
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
Life & Health Sciences > Psychology
Full Text Link: https://www.ncb ... les/PMC4024925/
Related URLs: http://www.pnas ... pnas.1318906111 (Publisher URL)
PURE Output Type: Article
Published Date: 2014-05-13
Published Online Date: 2014-04-22
Accepted Date: 2014-03-27
Authors: Li, X.
Wei, W.
Zhao, Q.-y.
Widagdo, J.
Baker-andresen, D.
Law, C. R. ( 0000-0003-0345-0237)
D'alessio, A.
Zhang, Y.
Bredy, T. W.

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