HDAC4 governs a transcriptional program essential for synaptic plasticity and memory.
Cell
; 151(4): 821-834, 2012 Nov 09.
Article
en En
| MEDLINE
| ID: mdl-23141539
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sinapsis
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Transcripción Genética
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Encéfalo
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Transporte Activo de Núcleo Celular
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Histona Desacetilasas
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Memoria
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Plasticidad Neuronal
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Neuronas
Límite:
Animals
Idioma:
En
Revista:
Cell
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos