Journal article
A transcription factor-binding domain of the coactivator CBP is essential for long-term memory and the expression of specific target genes
Learning & memory (Cold Spring Harbor, N.Y.), Vol.13(5), pp.609-617
2006
DOI: 10.1101/lm.213906
PMCID: PMC1783615
PMID: 16980541
Abstract
Transcriptional activation is a key process required for long-term memory formation. Recently, the transcriptional coactivator CREB-binding protein (CBP) was shown to be critical for hippocampus-dependent long-term memory and hippocampal synaptic plasticity. As a coactivator with intrinsic histone acetyltransferase activity, CBP interacts with numerous transcription factors and contains multiple functional domains. Currently, it is not known which transcription factor-binding domain of CBP is essential for memory storage. Using mice that carry inactivating mutations in the CREB-binding (KIX) domain of the coactivator CBP (
CBP
KIX/KIX
mice), we show that the KIX domain is required for long-term memory storage. These results are the first to identify an in vivo function for the KIX domain of CBP in the brain, and they suggest that KIX-interacting transcription factors recruit CBP histone acetyltransferase activity during long-term memory storage. One such KIX-interacting factor is the transcription factor CREB. Using quantitative real-time RT-PCR, we find that the expression of specific CREB target genes is reduced in the hippocampi of
CBP
KIX/KIX
mice during memory consolidation. The recruitment of the transcriptional coactivator CBP via the KIX domain thus imparts target gene-dependent selectivity to CREB-driven transcriptional regulation, thereby activating genes required for the long-term storage of hippocampus-dependent memory.
Details
- Title: Subtitle
- A transcription factor-binding domain of the coactivator CBP is essential for long-term memory and the expression of specific target genes
- Creators
- Marcelo A Wood - Department of Neurobiology & Behavior, Center for the Neurobiology of Learning & Memory, University of California at Irvine, Irvine, California 92697, USAMichelle A Attner - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USAAna M.M Oliveira - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USAPaul K Brindle - Department of Biochemistry, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, USATed Abel - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
- Resource Type
- Journal article
- Publication Details
- Learning & memory (Cold Spring Harbor, N.Y.), Vol.13(5), pp.609-617
- Publisher
- Cold Spring Harbor Laboratory Press
- DOI
- 10.1101/lm.213906
- PMID
- 16980541
- PMCID
- PMC1783615
- ISSN
- 1072-0502
- eISSN
- 1549-5485
- Alternative title
- CBP KIX domain is essential for long-term memory
- Language
- English
- Date published
- 2006
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984065832402771
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