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Series GSE76853 Query DataSets for GSE76853
Status Public on May 01, 2017
Title Acetyl-CoA metabolism by ACSS2 regulates neuronal histone acetylation and long-term memory [RNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Overall design 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).
Contributor(s) Mews P, Drake AM, Luczak V, Abel T, Berger SL
Citation(s) 28562591
Submission date Jan 13, 2016
Last update date May 15, 2019
Contact name Shelley L. Berger
Organization name University of Pennsylvania
Department Cell and Developmental Biology
Lab Berger
Street address 3400 CIVIC CENTER BLVD
City Philadelphia
State/province Pennsylvania
ZIP/Postal code 19104
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (16)
GSM2039053 Scramble control diff repeat 1
GSM2039054 ACL knockdown diff repeat 1
GSM2039055 ACSS2 knockdown diff repeat 1
This SubSeries is part of SuperSeries:
GSE76854 Acetyl-CoA metabolism by ACSS2 regulates neuronal histone acetylation and long-term memory
BioProject PRJNA308763
SRA SRP068435

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Supplementary file Size Download File type/resource
GSE76853_RAW.tar 383.6 Mb (http)(custom) TAR (of BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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