The DOI matches its Crossref record; 118 of the 118 references it cites were found in a registry or an index.
HDAC4 Governs a Transcriptional Program Essential for Synaptic Plasticity and Memory
Open accessAbstract
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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In the citing paper
“Nuclear HDAC4 functions as a transcriptional repressor, downregulating the expression of numerous plasticity-related genes, that may mediate effects on learning and memory impairment in mice.143,144”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [143]
In the citing paper
“the amount of synaptic proteins is regulated by transcription 102 , splicing 103 , mRNA transport 104 , translation 105 and degradation 106”
From Progress toward treatments for synaptic defects in autism (2013) · cites this paper as [102]
In the citing paper
“The subcellular localization of HDAC4 is thought to be regulated by NMDA receptors, as application of the NMDA receptor antagonist AP5 induces nuclear accumulation of HDAC4.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [60]
In the citing paper
“In the brain, HDAC4 also negatively regulates transcription required for synaptic transmission and information processing.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [60]
In the citing paper
“Transgenic mice expressing mutant HDAC4 with constitutive nuclear localization showed reduced expression of genes essential for synaptic function, including Camk2a, Homer1, and Snap25.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [60]
In the citing paper
“These mice in which nuclear HDAC4 functions as a gain-of-function suppressor of transcription showed abnormal acquisition and retention of memory.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [60]
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Citations
Cites
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The molecular basis of CaMKII function in synaptic and behavioural memory
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MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription
Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T. C., Qin, J., & Zoghbi, H. Y. (2008) · Science · doi:10.1126/science.1153252 · Cited by 1,823
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HDAC2 negatively regulates memory formation and synaptic plasticity
Guan, J.-S., Haggarty, S. J., Giacometti, E., Dannenberg, J.-H., Joseph, N., Gao, J., Nieland, T. J. F., Zhou, Y., Wang, X., Mazitschek, R., et al. (2009) · Nature · doi:10.1038/nature07925 · Cited by 1,644
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Bourgeron, T. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3992 · Cited by 975
From neural development to cognition: unexpected roles for chromatin
Ronan, J. L., Wu, W., & Crabtree, G. R. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3413 · Cited by 544
Milazzo, G., Mercatelli, D., Muzio, G. D., Triboli, L., Rosa, P. D., Perini, G., & Giorgi, F. M. (2020) · Genes · doi:10.3390/genes11050556 · Cited by 448
Nuclear calcium signalling in the regulation of brain function
Bading, H. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3531 · Cited by 381
DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways
Nardone, S., Sharan Sams, D., Reuveni, E., Getselter, D., Oron, O., Karpuj, M., & Elliott, E. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.70 · Cited by 266
Metadata
- Authors
- Sando, R., Gounko, N., Pieraut, S., Liao, L., Yates, J., & Maximov, A.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Maximov, Anton
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 151
- Issue
- 4
- Pages
- 821-834
- ISSN
- 0092-8674 (ISSN-L)
- 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
- 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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