CHD4

CHD4 Full Name

chromodomain helicase DNA binding protein 4

CHD4 Introduction

CHD4 (chromodomain helicase DNA binding protein 4) encodes an ATP-dependent chromatin remodeling enzyme that serves as the core subunit of the nucleosome remodeling and deacetylase (NuRD) complex. The protein belongs to the SNF2/RAD54 helicase family and contains multiple functional domains, including two PHD zinc fingers that recognize histone H3 tails, two chromodomains that interact with nucleosomal DNA, and a central ATPase/helicase domain that catalyzes nucleosome sliding. Through these domains, CHD4 modulates chromatin accessibility by repositioning nucleosomes, thereby regulating transcription factor access to target genes and maintaining genome structure. The protein is ubiquitously expressed across human tissues, with highest levels detected in thyroid, endometrium, and various cancer cell lines.

Figure 1. Structure of CHD4. CHD4 is composed of N terminal domain, PHD domain, Chromo domain, ATPase domain, and C-terminal domain.(Goswami K, 2025)

Dual Role in Transcriptional Regulation Through Distinct Complexes
CHD4 functions within two distinct macromolecular complexes to exert context-dependent effects on gene expression. As the core ATPase of the NuRD complex, CHD4 performs a dual regulatory function: it restricts chromatin accessibility across broad genomic regions to prevent non-specific transcription factor binding, while simultaneously maintaining accessibility at active enhancer and promoter regions to ensure precise transcriptional control. Acute depletion of CHD4 leads to immediate and widespread changes in chromatin accessibility, affecting over fifty thousand genomic sites within hours. Additionally, CHD4 operates within the ChAHP complex alongside ADNP and HP1 proteins, where it contributes to silencing of transposable elements and maintains cell fate plasticity by establishing inaccessible chromatin around specific DNA-binding sites independent of H3K9me3 modification.

Oncogenic Mechanisms in Cancer Progression
CHD4 exhibits oncogenic properties across multiple malignancies and serves as a critical driver of tumor metastasis. In gastric cancer, CHD4 is significantly overexpressed and correlates with advanced disease stages and poor prognosis. Mechanistically, CHD4 interacts with MYH9 via its ATPase domain, promoting MYH9 nuclear-to-cytoplasmic translocation and enabling MYH9 to orchestrate ubiquitination-dependent degradation of GSK3β. This process stabilizes β-catenin, leading to its nuclear accumulation and activation of downstream WNT target genes along with induction of epithelial-mesenchymal transition. In the immune context, CHD4 targeting impairs Foxp3+ regulatory T cell production and function while promoting anti-tumor immunity, suggesting that CHD4 inhibition may preferentially suppress tumor-associated Treg responses without inducing systemic autoimmunity. The protein is also implicated in breast cancer, colorectal cancer, hepatocellular carcinoma, and ovarian cancer progression.

Alternate Names for CHD4

CHD4; chromodomain helicase DNA binding protein 4; chromodomain-helicase-DNA-binding protein 4; Mi 2b; Mi2 BETA; CHD-4; ATP-dependent helicase CHD4; Mi-2 autoantigen 218 kDa protein; Mi-2b; Mi2-BETA; DKFZp686E06161;