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

Ruth M. Barrett, Melissa Malvaez, Eniko Kramar, Dina P. Matheos, Abraham Arrizon, Sara M. Cabrera, Gary Lynch, Robert W. Greene, Marcelo A. Wood

Research output: Contribution to journalArticle

131 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1545-1556
Number of pages12
JournalNeuropsychopharmacology
Volume36
Issue number8
DOIs
StatePublished - 2011

Fingerprint

Histone Code
CREB-Binding Protein
Long-Term Memory
Long-Term Potentiation
Histones
Hippocampus
Histone Acetyltransferases
Gene Expression
Neurons
Neuronal Plasticity
Acetylation
Lysine
Chromatin
Fear
Transcription Factors
Phosphorylation

Keywords

  • CBP
  • histone acetylation
  • long-term memory
  • long-term potentiation

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Barrett, R. M., Malvaez, M., Kramar, E., Matheos, D. P., Arrizon, A., Cabrera, S. M., ... Wood, M. A. (2011). Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory. Neuropsychopharmacology, 36(8), 1545-1556. https://doi.org/10.1038/npp.2011.61

Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory. / Barrett, Ruth M.; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P.; Arrizon, Abraham; Cabrera, Sara M.; Lynch, Gary; Greene, Robert W.; Wood, Marcelo A.

In: Neuropsychopharmacology, Vol. 36, No. 8, 2011, p. 1545-1556.

Research output: Contribution to journalArticle

Barrett, RM, Malvaez, M, Kramar, E, Matheos, DP, Arrizon, A, Cabrera, SM, Lynch, G, Greene, RW & Wood, MA 2011, 'Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory', Neuropsychopharmacology, vol. 36, no. 8, pp. 1545-1556. https://doi.org/10.1038/npp.2011.61
Barrett, Ruth M. ; Malvaez, Melissa ; Kramar, Eniko ; Matheos, Dina P. ; Arrizon, Abraham ; Cabrera, Sara M. ; Lynch, Gary ; Greene, Robert W. ; Wood, Marcelo A. / Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory. In: Neuropsychopharmacology. 2011 ; Vol. 36, No. 8. pp. 1545-1556.
@article{ac37bfe26c9145dcb1ae967514e5634d,
title = "Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory",
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.",
keywords = "CBP, histone acetylation, long-term memory, long-term potentiation",
author = "Barrett, {Ruth M.} and Melissa Malvaez and Eniko Kramar and Matheos, {Dina P.} and Abraham Arrizon and Cabrera, {Sara M.} and Gary Lynch and Greene, {Robert W.} and Wood, {Marcelo A.}",
year = "2011",
doi = "10.1038/npp.2011.61",
language = "English (US)",
volume = "36",
pages = "1545--1556",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory

AU - Barrett, Ruth M.

AU - Malvaez, Melissa

AU - Kramar, Eniko

AU - Matheos, Dina P.

AU - Arrizon, Abraham

AU - Cabrera, Sara M.

AU - Lynch, Gary

AU - Greene, Robert W.

AU - Wood, Marcelo A.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - CBP

KW - histone acetylation

KW - long-term memory

KW - long-term potentiation

UR - http://www.scopus.com/inward/record.url?scp=85027948621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027948621&partnerID=8YFLogxK

U2 - 10.1038/npp.2011.61

DO - 10.1038/npp.2011.61

M3 - Article

VL - 36

SP - 1545

EP - 1556

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 8

ER -