Title: | Acetyl-CoA metabolism by ACSS2 regulates neuronal histone acetylation and long-term memory [RNA-seq]
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dateReleased: |
05-01-2017
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description: |
Metabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and direct regulator of histone acetylation in neurons and of long-term mammalian memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory. These results reveal a unique connection between cellular metabolism and neural plasticity, and establish a link between generation of acetyl-CoA and neuronal chromatin regulation. Global survey of gene expression in CAD cells and differentiated CAD neurons following lentiviral knockdown of ACSS2 or ATP citrate lyase (ACL) (and control = scramble hairpin); survey of hippocampal gene expression changes associated with retrieval of fear memory, after ACSS2-AAV knockdown or in EGFP-AAV control (comparison of 0h vs. 1h post-memory retrieval).
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privacy: |
not applicable
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aggregation: |
instance of dataset
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ID: |
E-GEOD-76853
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refinement: |
raw
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alternateIdentifiers: |
76853
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keywords: |
functional genomics
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dateModified: |
05-07-2017
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availability: |
available
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types: |
gene expression
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name: |
Mus musculus
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accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-76853/E-GEOD-76853.raw.1.zip |
storedIn: |
ArrayExpress
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qualifier: |
gzip compressed
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format: |
TXT
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accessType: |
download
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authentication: |
none
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authorization: |
none
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accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-76853/E-GEOD-76853.processed.1.zip |
storedIn: |
ArrayExpress
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qualifier: |
gzip compressed
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format: |
TXT
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accessType: |
download
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authentication: |
none
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authorization: |
none
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accessURL: | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76853 |
storedIn: |
Gene Expression Omnibus
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qualifier: |
not compressed
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format: |
HTML
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accessType: |
landing page
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primary: |
true
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authentication: |
none
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authorization: |
none
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abbreviation: |
EBI
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homePage: | http://www.ebi.ac.uk/ |
ID: |
SCR:004727
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name: |
European Bioinformatics Institute
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homePage: | https://www.ebi.ac.uk/arrayexpress/ |
ID: |
SCR:002964
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name: |
ArrayExpress
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