Tet1 Is Critical for Neuronal Activity-Regulated Gene Expression and Memory Extinction
The ten-eleven translocation (Tet) family of methylcytosine dioxygenases catalyze oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and promote DNA demethylation. Despite the abundance of 5hmC and Tet proteins in the brain, little is known about the functions of the neuronal Tet...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/102511 https://orcid.org/0000-0003-1262-0592 |
| _version_ | 1826205111452434432 |
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| author | Rudenko, Andrii Dawlaty, Meelad M. Seo, Jinsoo Cheng, Albert W. Meng, Jia Le, Thuc Faull, Kym F. Jaenisch, Rudolf Tsai, Li-Huei |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Rudenko, Andrii Dawlaty, Meelad M. Seo, Jinsoo Cheng, Albert W. Meng, Jia Le, Thuc Faull, Kym F. Jaenisch, Rudolf Tsai, Li-Huei |
| author_sort | Rudenko, Andrii |
| collection | MIT |
| description | The ten-eleven translocation (Tet) family of methylcytosine dioxygenases catalyze oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and promote DNA demethylation. Despite the abundance of 5hmC and Tet proteins in the brain, little is known about the functions of the neuronal Tet enzymes. Here, we analyzed Tet1 knockout mice (Tet1KO) and found downregulation of multiple neuronal activity-regulated genes, including Npas4, c-Fos, and Arc. Furthermore, Tet1KO animals exhibited abnormal hippocampal long-term depression and impaired memory extinction. Analysis of the key regulatory gene, Npas4, indicated that its promoter region, containing multiple CpG dinucleotides, is hypermethylated in both naive Tet1KO mice and after extinction training. Such hypermethylation may account for the diminished expression of Npas4 itself and its downstream targets, impairing transcriptional programs underlying cognitive processes. In summary, we show that neuronal Tet1 regulates normal DNA methylation levels, expression of activity-regulated genes, synaptic plasticity, and memory extinction. |
| first_indexed | 2024-09-23T13:07:13Z |
| format | Article |
| id | mit-1721.1/102511 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:07:13Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1025112022-09-28T12:07:59Z Tet1 Is Critical for Neuronal Activity-Regulated Gene Expression and Memory Extinction Rudenko, Andrii Dawlaty, Meelad M. Seo, Jinsoo Cheng, Albert W. Meng, Jia Le, Thuc Faull, Kym F. Jaenisch, Rudolf Tsai, Li-Huei Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Whitehead Institute for Biomedical Research Rudenko, Andrii Seo, Jinsoo Meng, Jia Jaenisch, Rudolf Tsai, Li-Huei The ten-eleven translocation (Tet) family of methylcytosine dioxygenases catalyze oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and promote DNA demethylation. Despite the abundance of 5hmC and Tet proteins in the brain, little is known about the functions of the neuronal Tet enzymes. Here, we analyzed Tet1 knockout mice (Tet1KO) and found downregulation of multiple neuronal activity-regulated genes, including Npas4, c-Fos, and Arc. Furthermore, Tet1KO animals exhibited abnormal hippocampal long-term depression and impaired memory extinction. Analysis of the key regulatory gene, Npas4, indicated that its promoter region, containing multiple CpG dinucleotides, is hypermethylated in both naive Tet1KO mice and after extinction training. Such hypermethylation may account for the diminished expression of Npas4 itself and its downstream targets, impairing transcriptional programs underlying cognitive processes. In summary, we show that neuronal Tet1 regulates normal DNA methylation levels, expression of activity-regulated genes, synaptic plasticity, and memory extinction. Brain & Behavior Research Foundation (Young Investigator Award) National Institutes of Health (U.S.) (Grant RO1 NS078839) 2016-05-16T13:55:09Z 2016-05-16T13:55:09Z 2013-09 Article http://purl.org/eprint/type/JournalArticle 08966273 1097-4199 http://hdl.handle.net/1721.1/102511 Rudenko, Andrii, Meelad M. Dawlaty, Jinsoo Seo, Albert W. Cheng, Jia Meng, Thuc Le, Kym F. Faull, Rudolf Jaenisch, and Li-Huei Tsai. “Tet1 Is Critical for Neuronal Activity-Regulated Gene Expression and Memory Extinction.” Neuron 79, no. 6 (September 2013): 1109–22. https://orcid.org/0000-0003-1262-0592 en_US http://dx.doi.org/10.1016/j.neuron.2013.08.003 Neuron Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Rudenko, Andrii Dawlaty, Meelad M. Seo, Jinsoo Cheng, Albert W. Meng, Jia Le, Thuc Faull, Kym F. Jaenisch, Rudolf Tsai, Li-Huei Tet1 Is Critical for Neuronal Activity-Regulated Gene Expression and Memory Extinction |
| title | Tet1 Is Critical for Neuronal Activity-Regulated Gene Expression and Memory Extinction |
| title_full | Tet1 Is Critical for Neuronal Activity-Regulated Gene Expression and Memory Extinction |
| title_fullStr | Tet1 Is Critical for Neuronal Activity-Regulated Gene Expression and Memory Extinction |
| title_full_unstemmed | Tet1 Is Critical for Neuronal Activity-Regulated Gene Expression and Memory Extinction |
| title_short | Tet1 Is Critical for Neuronal Activity-Regulated Gene Expression and Memory Extinction |
| title_sort | tet1 is critical for neuronal activity regulated gene expression and memory extinction |
| url | http://hdl.handle.net/1721.1/102511 https://orcid.org/0000-0003-1262-0592 |
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