Cited by 243Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchGenomics and Chromatin Dynamics

Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory

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Barrett, Ruth M, Malvaez, Melissa, Kramar, Eniko, Matheos, Dina P, Arrizon, Abraham, Cabrera, Sara M, Lynch, Gary, Greene, Robert W +1 more·2011·Neuropsychopharmacology

Abstract

To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories.

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Authors
Barrett, R. M., Malvaez, M., Kramar, E., Matheos, D. P., Arrizon, A., Cabrera, S. M., Lynch, G., Greene, R. W., & Wood, M. A.
Affiliations
  • University of California, Irvine (US)
  • Allergan (United States) (US)
  • Dallas VA Medical Center (US)
Corresponding author
Wood, Marcelo A
Venue
Neuropsychopharmacology
Published
2011-04-20
Volume
36
Issue
8
Pages
1545-1556
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
OpenAlex
W1963551704
Cited by
243
References
70
Citations by year
2026: 8 · 2025: 8 · 2024: 22 · 2023: 9 · 2022: 18 · 2021: 14 · 2020: 17 · 2019: 17 · 2018: 6 · 2017: 14 · 2016: 23 · 2015: 9 · 2014: 28 · 2013: 28 · 2012: 14
FWCI
12.67
Type
journal article
Language
en
Open access
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • Whitehall Foundation
  • Multidisciplinary University Research Initiative
  • Office of Naval Research
  • National Institute of Mental Health (R01MH080297, R01MH081004, F31MH85494, F31MH085494)
  • National Institute on Drug Abuse (F31DA293682, F31DA029368)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
CREB-binding protein, histone acetylation, histone modifications, hippocampal CA1, long-term potentiation, long-term memory, memory consolidation, CREB phosphorylation, P300, contextual fear memory, object recognition memory, synaptic plasticity, chromatin modification
MeSH terms
Animals, Hippocampus, Histones, Mice, Inbred C57BL, Long-Term Potentiation, Mice, Knockout, CREB-Binding Protein, Mice, Memory, Long-Term

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