CHD4

CHD4, also known as Mi-2β, is a human gene encoding an ATP-dependent chromatin remodeler in the CHD (chromodomain helicase DNA-binding) family. The encoded protein is a core component of the Mi-2/NuRD complex, a multi-subunit assembly that couples nucleosome remodeling with histone deacetylation to repress transcription.

CHD4 contains an ATPase/helicase motor of the SNF2 family and two N-terminal chromodomains, enabling it to read histone methylation marks and remodel chromatin in an ATP-dependent manner. In NuRD, CHD4 cooperates with other subunits such as MTA proteins, RBBP4/7, and GATAD2, recruiting the complex to chromatin and facilitating transcriptional silencing during development, differentiation, and cellular stress responses. The NuRD complex integrates chromatin remodeling with deacetylation, linking chromatin structure to transcriptional control.

In development and biology, CHD4 is required for proper lineage specification, embryonic development, and DNA damage response. It participates in regulation of pluripotency, differentiation, and genomic stability. Altered CHD4 function can disrupt gene expression programs and chromatin organization.

Clinically, germline or somatic CHD4 variants have been associated with neurodevelopmental disorders characterized by intellectual disability, hypotonia, and facial or congenital anomalies. CHD4 dysregulation has also been observed in various cancers and is thought to influence tumor suppressor pathways, differentiation, and DNA damage signaling.