First Author | Li X | Year | 2014 |
Journal | Proc Natl Acad Sci U S A | Volume | 111 |
Issue | 19 | Pages | 7120-5 |
PubMed ID | 24757058 | Mgi Jnum | J:211080 |
Mgi Id | MGI:5573103 | Doi | 10.1073/pnas.1318906111 |
Citation | Li X, et al. (2014) Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation. Proc Natl Acad Sci U S A 111(19):7120-5 |
abstractText | 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. |