Neuronal CTCF Is Necessary for Basal and Experience-Dependent Gene Regulation, Memory Formation, and Genomic Structure of BDNF and Arc.
Cell Rep
; 17(9): 2418-2430, 2016 11 22.
Article
en En
| MEDLINE
| ID: mdl-27880914
ABSTRACT
CCCTC-binding factor (CTCF) is an organizer of higher-order chromatin structure and regulates gene expression. Genetic studies have implicated mutations in CTCF in intellectual disabilities. However, the role of CTCF-mediated chromatin structure in learning and memory is unclear. We show that depletion of CTCF in postmitotic neurons, or depletion in the hippocampus of adult mice through viral-mediated knockout, induces deficits in learning and memory. These deficits in learning and memory at the beginning of adulthood are correlated with impaired long-term potentiation and reduced spine density, with no changes in basal synaptic transmission and dendritic morphogenesis and arborization. Cognitive disabilities are associated with downregulation of cadherin and learning-related genes. In addition, CTCF knockdown attenuates fear-conditioning-induced hippocampal gene expression of key learning genes and loss of long-range interactions at the BDNF and Arc loci. This study thus suggests that CTCF-dependent gene expression regulation and genomic organization are regulators of learning and memory.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
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Genoma
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Factor Neurotrófico Derivado del Encéfalo
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Proteínas del Citoesqueleto
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Factor de Unión a CCCTC
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Memoria
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Proteínas del Tejido Nervioso
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Neuronas
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2016
Tipo del documento:
Article
País de afiliación:
Israel