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

Li, Xiang, Wei, Wei, Zhao, Qiong-Yi, Widagdo, Jocelyn, Baker-Andresen, Danay, Flavell, Charlotte R., D'Alessio, Ana, Zhang, Yi and Bredy, Timothy W. (2014) Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation. Proceedings of the National Academy of Sciences, 111 19: 7120-7125. doi:10.1073/pnas.1318906111

Author Li, Xiang
Wei, Wei
Zhao, Qiong-Yi
Widagdo, Jocelyn
Baker-Andresen, Danay
Flavell, Charlotte R.
D'Alessio, Ana
Zhang, Yi
Bredy, Timothy W.
Title Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation
Journal name Proceedings of the National Academy of Sciences   Check publisher's open access policy
ISSN 0027-8424
Publication date 2014-05-13
Sub-type Article (original research)
DOI 10.1073/pnas.1318906111
Open Access Status DOI
Volume 111
Issue 19
Start page 7120
End page 7125
Total pages 6
Editor James L. McGaugh
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Formatted 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.

Significance: We have discovered a critical role for ten-eleven translocation 3-mediated hydroxylation of 5-methycytosine in the adult prefrontal cortex in mediating rapid behavioral adaptation. 5-hydroxymethylcytosine (5-hmC) is highly dynamic in response to fear extinction training, and rather than simply reflecting a functional intermediary of active DNA demethylation, the learning-induced intergenic accumulation of 5-hmC creates an epigenetic state that promotes experience-dependent gene expression and behavioral adaptation.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
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Citation counts: TR Web of Science Citation Count  Cited 63 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 12 May 2014, 07:36:18 EST by Qiongyi Zhao on behalf of Queensland Brain Institute