CHD4 (Chromodomain Helicase DNA-Binding Protein 4), also known as Mi-2 beta, is an ATP-dependent chromatin remodeler and core component of the NuRD (Nucleosome Remodeling Deacetylase) complex [1][2]. This protein plays critical roles in transcriptional repression, chromatin dynamics, and DNA damage response in neurons [4]. CHD4 dysfunction has been implicated in Alzheimer's disease [3], Parkinson's disease, and various cancers [2]. [1]
CHD4 protein is a member of the chromodomain helicase family (CHD), characterized by tandem chromodomains that recognize methylated histone tails and a SNF2-type ATPase domain that provides chromatin remodeling activity [13]. As the catalytic engine of the NuRD complex, CHD4 coordinates both ATP-dependent nucleosome sliding and histone deacetylase (HDAC) activities to repress gene expression. In the nervous system, CHD4 regulates genes involved in synaptic plasticity, neuronal survival, and inflammatory responses [11][12]. [2]
| Property | Value |
|---|---|
| Protein Name | CHD4 (Mi-2 Beta) |
| Gene | CHD4 |
| UniProt ID | Q14839 |
| PDB ID | 5O9G, 6CP6 |
| Molecular Weight | 226 kDa |
| Subcellular Localization | Nucleus (chromatin-associated) |
| Protein Family | CHD family, SNF2 superfamily |
| Aliases | Mi-2 beta, CHDR1, CHD4 |
CHD4 protein contains multiple functional domains [1]:
The ATPase domain adopts a RecA-like fold typical of chromatin remodelers, with two RecA homology domains connected by a hinge region that allows conformational changes during the remodeling cycle.
CHD4 in the nervous system [4][5]:
CHD4 contributes to AD pathogenesis through [3][8]:
CHD16 involvement in PD [16]:
CHD4 mutations are common in cancers [2]:
CHD4 is being explored as a therapeutic target [9][10]:
Kelley et al. CHD4 regulates DNA damage response in neurons, Nat Neurosci (2019). 2019. ↩︎
Yamada et al. CHD4 regulates neuronal gene expression and survival, J Neurosci (2013). 2013. ↩︎