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E-GEOD-76850 - Acetyl-CoA metabolism by ACSS2 regulates neuronal histone acetylation and long-term memory [ChIP-seq]

Status
Released on 1 May 2017, last updated on 7 May 2017
Organism
Mus musculus
Samples (14)
Protocols (4)
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 directchum 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. Genome-wide examination of histone H3 and H4 acetylation, as well as ACSS2 binding, in undifferentiated CAD cells and differentiated CAD neurons; background adjusted by H3 ChIP or Input.
Experiment type
ChIP-seq 
Contacts
Shelley L. Berger <bergers@mail.med.upenn.edu>, Adam M Drake, Philipp Mews, Shelley L Berger, Ted Abel, Vincent Luczak
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
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