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TET1 Controls CNS 5-Methylcytosine Hydroxylation, Active DNA Demethylation, Gene Transcription, and Memory Formation
Open accessAbstract
Summary Dynamic changes in 5-methylcytosine (5mC) have been implicated in the regulation of gene expression critical for consolidation of memory. However, little is known about how these changes in 5mC are regulated in the adult brain. The enzyme Tet methylcytosine dioxygenase 1 (TET1) has been shown to promote active DNA demethylation in the nervous system. Therefore, we took a viral-mediated approach to overexpress the enzyme in the hippocampus and test its potential involvement in memory formation. We found that Tet1 is a neuronal-activity regulated gene and that its overexpression leads to changes in global modified cytosine levels. Furthermore, expression of TET1 or a catalytically inactive mutant (TET1m) resulted in the up-regulation of several neuronal memory-associated genes and impaired contextual fear memory. In summary, we show that neuronal Tet1 regulates DNA methylation levels and that its expression, independent of its catalytic activity, regulates the expression of CNS activity- dependent genes and memory formation.
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Metadata
- Authors
- Kaas, G. A., Zhong, C., Eason, D. E., Ross, D. L., Vachhani, R. V., Ming, G.-L., King, J. R., Song, H., & Sweatt, J. D.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 79
- Issue
- 6
- Pages
- 1086-1093
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2018338317
- Cited by
- 414
- References
- 5
- FWCI
- 18.56
- Type
- journal article
- Language
- en
- Open access
- bronze
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