Class IIa HDACs regulate learning and memory through dynamic experience-dependent repression of transcription.
Animals
Behavior, Animal
/ physiology
Cell Nucleus
/ metabolism
Cells, Cultured
Cerebral Cortex
/ cytology
Epigenetic Repression
/ physiology
Female
HEK293 Cells
Histone Deacetylases
/ metabolism
Humans
Male
Memory
/ physiology
Mice
Mice, Knockout
Neurons
Primary Cell Culture
Signal Transduction
/ genetics
Spatio-Temporal Analysis
Transcription, Genetic
/ physiology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 08 2019
02 08 2019
Historique:
received:
15
03
2019
accepted:
13
07
2019
entrez:
4
8
2019
pubmed:
4
8
2019
medline:
18
12
2019
Statut:
epublish
Résumé
The formation of new memories requires transcription. However, the mechanisms that limit signaling of relevant gene programs in space and time for precision of information coding remain poorly understood. We found that, during learning, the cellular patterns of expression of early response genes (ERGs) are regulated by class IIa HDACs 4 and 5, transcriptional repressors that transiently enter neuronal nuclei from cytoplasm after sensory input. Mice lacking these repressors in the forebrain have abnormally broad experience-dependent expression of ERGs, altered synaptic architecture and function, elevated anxiety, and severely impaired memory. By acutely manipulating the nuclear activity of class IIa HDACs in behaving animals using a chemical-genetic technique, we further demonstrate that rapid induction of transcriptional programs is critical for memory acquisition but these programs may become dispensable when a stable memory is formed. These results provide new insights into the molecular basis of memory storage.
Identifiants
pubmed: 31375688
doi: 10.1038/s41467-019-11409-0
pii: 10.1038/s41467-019-11409-0
pmc: PMC6677776
doi:
Substances chimiques
Hdac5 protein, mouse
EC 3.5.1.98
Histone Deacetylases
EC 3.5.1.98
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3469Subventions
Organisme : NIGMS NIH HHS
ID : P41 GM103412
Pays : United States
Organisme : NIH HHS
ID : S10 OD021784
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM117049
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH118442
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS087026
Pays : United States
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