Crebbp Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
CREBBP (CREB Binding Protein) is a transcriptional coactivator that acetylates histones and transcription factors. It plays essential roles in learning, memory, and neuronal survival. Mutations cause Rubinstein-Taybi syndrome and implicate the gene in Alzheimer's and Huntington's diseases.
| Attribute |
Value |
| Gene Symbol |
CREBBP |
| Full Name |
CREB Binding Protein |
| Chromosomal Location |
16p13.3 |
| NCBI Gene ID |
1387 |
| OMIM |
600140 |
| Ensembl ID |
ENSG00000105383 |
| UniProt ID |
Q92793 (CREBBP) |
CREBBP encodes a histone acetyltransferase (HAT) that:
- Acetylates histones H3/H4 to open chromatin
- Acetylates transcription factors (p53, NF-κB, CREB)
- Functions as transcriptional coactivator
- Essential for:
- Learning and memory
- Synaptic plasticity
- Neuronal survival
- Embryonic development
- Interacts with CBP (they are the same protein)
- CREBBP/CBP levels decline in AD brain
- Essential for memory consolidation
- Acetylates tau and reduces aggregation
- May be therapeutic target
- Mutant huntingtin sequesters CREBBP
- Contributes to transcriptional dysregulation
- Restoring CREBBP function is therapeutic strategy
- Heterozygous CREBBP mutations cause RTS
- Intellectual disability, distinctive features
- Haploinsufficiency
CREBBP is expressed in:
- Brain: Cortex, hippocampus, cerebellum
- Ubiquitously in peripheral tissues
- Nuclear localization
- HDAC inhibitors: Increase histone acetylation
- CBP activators: Under development
- Gene therapy: AAV-CREBBP for neuroprotection
CREBBP shows broad expression across tissues:
- Brain: High in cerebral cortex, hippocampus (CA1-CA3), cerebellum (Purkinje cells)
- Neurons: Expressed in most neuronal subtypes including pyramidal cells, interneurons
- Glia: Present in astrocytes and microglia
- Peripheral: Liver (highest), kidney, heart, lung, skeletal muscle
CREBBP (CREB-binding protein) is a master transcriptional coactivator:
-
Histone Acetyltransferase (HAT) Activity:
- Acetylates histone H3K27, H3K9
- Remodels chromatin for transcription
- HAT activity required for learning/memory
-
Transcriptional Coactivator:
- Interacts with CREB, p53, NF-κB, HIF-1α
- Bridges transcription factors to basal machinery
- Essential for activity-dependent gene expression
-
CRD Complex (CBP/p300):
- Forms heterodimers with p300
- Multiple domains for protein interactions
- Bromodomain recognizes acetyl-lysine
-
Signal Integration:
- Integrates cAMP, calcium, growth factor signals
- Coordinates transcriptional responses
- Dysregulation affects neuroplasticity
- Alzheimer's Disease: Reduced CBP in neurons, therapeutic potential
- Huntington's Disease: Mutant HTT sequesters CBP
- FTD/ALS: TDP-43 affects CBP function
Key findings from model systems:
- Heterozygous knockout mice: Viable, model for Rubinstein-Taybi syndrome
- Neuron-specific knockouts: Severe memory deficits, impaired LTP
- Conditional knockouts: Reversible deficits
- Knock-in models: Disease-causing mutations recapitulate phenotype
- Rescue studies: Demonstrate CBP haploinsufficiency role
CREBBP is a therapeutic target:
- HDAC inhibitors: Increase histone acetylation, may compensate
- Small molecule activators: HAT activity enhancers in development
- Gene therapy: AAV-CREBBP delivery being explored
- Combination approaches: With neurotrophic factors
- Rouaux C, et al. (2004) CBP loss induces transcriptional dysregulation in Huntington's disease. EMBO J 23:3143-3153. PMID:15241480
- Valor LM, et al. (2013) Selective contributions of CBP and p300 to Huntington's disease. Nat Neurosci 16:1291-1300. PMID:23911789
The study of Crebbp Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
[1] Goodman RH, Smolik S. (2000). CBP/p300 in cell growth, transformation, and development. Genes Dev. 14(13):1553-1577. PMID:10859150
[2] Kalkhoven E. (2004). CBP and p300: HATs for different occasions. Biochem Pharmacol. 68(6):1145-1155. PMID:15313432
[3] Veitia RA. (2003). Balancing acts: the role of transcriptional coactivators in disease. Trends Genet. 19(5):263-268. PMID:12711215