Cited by 277Histone Deacetylase Inhibitors ResearchNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

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HDAC4 Governs a Transcriptional Program Essential for Synaptic Plasticity and Memory

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Sando, Richard, Gounko, Natalia, Pieraut, Simon, Liao, Lujian, Yates, John, Maximov, Anton·2012·Cell

DOI 10.1016/j.cell.2012.09.037PMC PMC3496186

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Abstract

Neuronal activity influences genes involved in circuit development and information processing. However, the molecular basis of this process remains poorly understood. We found that HDAC4, a histone deacetylase that shuttles between the nucleus and cytoplasm, controls a transcriptional program essential for synaptic plasticity and memory. The nuclear import of HDAC4 and its association with chromatin is negatively regulated by NMDA receptors. In the nucleus, HDAC4 represses genes encoding constituents of central synapses, thereby affecting synaptic architecture and strength. Furthermore, we show that a truncated form of HDAC4 encoded by an allele associated with mental retardation is a gain-of-function nuclear repressor that abolishes transcription and synaptic transmission despite the loss of the deacetylase domain. Accordingly, mice carrying a mutant that mimics this allele exhibit deficits in neurotransmission, spatial learning, and memory. These studies elucidate a mechanism of experience-dependent plasticity and define the biological role of HDAC4 in the brain.

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Authors: Sando, R., Gounko, N., Pieraut, S., Liao, L., Yates, J., & Maximov, A.
Affiliations: Scripps Research Institute (US)
Corresponding author: Maximov, Anton
ORCID: Sando, Richard
Gounko, Natalia
Pieraut, Simon
Liao, Lujian
Yates, John
Maximov, Anton
Venue: Cell
Publisher: Elsevier BV
Published: 2012-11
Volume: 151
Issue: 4
Pages: 821-834
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2012.09.037
PMC: PMC3496186
OpenAlex: W2031926951
Cited by: 274
References: 118
Citations by year: 2026: 9 · 2025: 17 · 2024: 23 · 2023: 18 · 2022: 19 · 2021: 22 · 2020: 20 · 2019: 24 · 2018: 21 · 2017: 17 · 2016: 23 · 2015: 22 · 2014: 25 · 2013: 14
FWCI: 7.85
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 373 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Lirias (submittedVersion)
Funders: National Institute of Mental Health (MH085776, R01MH085776, R01MH067880, MH067880-09)
National Institute of Neurological Disorders and Stroke (P30NS057096, NS057096)
National Center for Research Resources (P41RR011823, RR011823)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: HDAC4, histone deacetylase, synaptic plasticity, memory, NMDA receptor, nuclear import, chromatin, transcriptional repression, central synapses, intellectual disability, neurotransmission, spatial learning, experience-dependent plasticity
MeSH terms: Animals, Brain, Histone Deacetylases, Memory, Neuronal Plasticity, Neurons, Synapses, Transcription Factors, Transcription, Genetic, Receptors, N-Methyl-D-Aspartate, Prosencephalon, Active Transport, Cell Nucleus, Mice

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HDAC4 Governs a Transcriptional Program Essential for Synaptic Plasticity and Memory

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