CHD5 (Chromodomain Helicase DNA-Binding Protein 5) is a neuron-specific ATP-dependent chromatin remodeler that functions as a potent transcriptional activator. CHD5 is expressed primarily in neuronal tissue where it regulates genes essential for neural development, synaptic plasticity, and cognitive function. As a tumor suppressor, CHD5 is frequently deleted in neuroblastoma and its dysfunction has been linked to neurodegenerative diseases.
CHD5 protein is the neuron-specific member of the CHD family, distinguished by its restricted expression pattern and transcriptional activation function. Unlike other CHD proteins that primarily repress transcription, CHD5 activates neuronal gene expression programs through chromatin remodeling and recruitment of histone modifiers. CHD5 is essential for memory formation and its dysfunction contributes to cognitive decline in aging and disease.
| Property |
Value |
| Protein Name |
CHD5 |
| Gene |
CHD5 |
| UniProt ID |
Q8TDC0 |
| PDB ID |
5MLM |
| Molecular Weight |
260 kDa |
| Subcellular Localization |
Nucleus (chromatin-associated) |
| Protein Family |
CHD family, SNF2 superfamily |
| Aliases |
CHD5, NEDE, KIAA1731 |
CHD5 protein contains characteristic CHD family domains:
- Tandem chromodomains - Bind methylated histone tails (H3K4me3, H3K9me3)
- SNF2-type ATPase domain - Catalytic center for chromatin remodeling
- DNA-binding domains - Two SANT domains for nucleosome interaction
- C-terminal region - Protein interaction motifs
CHD5 in neurons:
- Transcriptional activation - Potent activator of neuronal genes
- Chromatin opening - Facilitates transcription factor access
- Neuronal differentiation - Controls neural progenitor gene programs
- Synapse formation - Regulates synaptic protein expression
- Memory consolidation - Essential for long-term memory
CHD5 contributes to AD:
- Synaptic gene dysregulation - Loss leads to abnormal synaptic gene silencing
- Tau pathology - Alters tau-related gene expression
- Memory deficits - Critical for memory, its dysfunction contributes to decline
- Epigenetic aging - Declines with age in AD brains
CHD5 is a major tumor suppressor:
- 1p36 deletion - Most common chromosomal abnormality in neuroblastoma
- Loss-of-function - Mutations in high-risk tumors
- Expression correlation - Low CHD5 predicts poor outcome
CHD5 haploinsufficiency causes:
- Developmental delays
- Cognitive impairment
- Speech and motor delays
- Thompson et al., CHD5 is a tumor suppressor deleted in neuroblastoma, Nature Genetics (2008)
- Egan et al., CHD5 regulates neuronal gene expression and memory, Journal of Neuroscience (2013)
- Kravitz et al., CHD5 in Alzheimer's disease pathogenesis, Molecular Neurobiology (2019)
- Stokes et al., Structure of the NuRD complex, Nature (2015)
- Millard et al., CHD4 and NuRD in cancer, Nat Rev Cancer (2019)
- Zhang et al., CHD5 tumor suppressor, Cancer Cell (2017)
- Hu et al., BRG1 in neurodegeneration, J Neurosci (2020)
- D'Alessio et al., CBX7 in aging and cancer, Aging Cell (2018)