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

X. Li, W. Wei, Q.-y. Zhao, J. Widagdo, D. Baker-andresen, C. R. Law, A. D'alessio, Y. Zhang, T. W. Bredy

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)7120-7125
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number19
Early online date22 Apr 2014
Publication statusPublished - 13 May 2014


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