Title |
Acetyl-CoA synthetase regulates histone acetylation and hippocampal memory
|
---|---|
Published in |
Nature, May 2017
|
DOI | 10.1038/nature22405 |
Pubmed ID | |
Authors |
Philipp Mews, Greg Donahue, Adam M. Drake, Vincent Luczak, Ted Abel, Shelley L. Berger |
Abstract |
Metabolic production of acetyl coenzyme A (acetyl-CoA) is linked to histone acetylation and gene regulation, but the precise mechanisms of this process are largely unknown. Here we show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) directly regulates histone acetylation in neurons and spatial memory in mammals. In a neuronal cell culture model, ACSS2 increases in the nuclei of differentiating neurons and localizes to upregulated neuronal genes near sites of elevated histone acetylation. A decrease in ACSS2 lowers nuclear acetyl-CoA levels, histone acetylation, and responsive expression of the cohort of neuronal genes. In adult mice, attenuation of hippocampal ACSS2 expression impairs long-term spatial memory, a cognitive process that relies on histone acetylation. A decrease in ACSS2 in the hippocampus also leads to defective upregulation of memory-related neuronal genes that are pre-bound by ACSS2. These results reveal a connection between cellular metabolism, gene regulation, and neural plasticity and establish a link between acetyl-CoA generation 'on-site' at chromatin for histone acetylation and the transcription of key neuronal genes. |
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United Kingdom | 10 | 5% |
France | 6 | 3% |
Spain | 4 | 2% |
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Germany | 3 | 2% |
India | 3 | 2% |
Canada | 3 | 2% |
China | 2 | 1% |
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Demographic breakdown
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Scientists | 51 | 28% |
Science communicators (journalists, bloggers, editors) | 5 | 3% |
Practitioners (doctors, other healthcare professionals) | 2 | 1% |
Mendeley readers
Geographical breakdown
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---|---|---|
United States | 3 | <1% |
Unknown | 508 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 132 | 26% |
Researcher | 69 | 14% |
Student > Bachelor | 57 | 11% |
Student > Master | 43 | 8% |
Student > Doctoral Student | 28 | 5% |
Other | 78 | 15% |
Unknown | 104 | 20% |
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Pharmacology, Toxicology and Pharmaceutical Science | 11 | 2% |
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