CHD4

CHD4

CHD4 (Chromodomain Helicase DNA Binding Protein 4) is a protein that in humans is encoded by the CHD4 gene. It is a member of the chromodomain helicase DNA-binding (CHD) family of proteins, which are involved in chromatin remodeling and transcriptional regulation. CHD4 is a critical component of the nucleosome remodeling and deacetylase (NuRD) complex, which plays a significant role in gene expression regulation, DNA repair, and cell cycle progression.

Function

CHD4 is primarily known for its role in the NuRD complex, where it functions as an ATP-dependent chromatin remodeler. This activity allows CHD4 to alter chromatin structure, thereby influencing the accessibility of DNA to transcription factors and other DNA-binding proteins. The remodeling of chromatin by CHD4 is essential for the repression of gene expression, particularly in the context of development and differentiation.

In addition to its role in transcriptional repression, CHD4 is involved in DNA damage response. It is recruited to sites of DNA damage, where it facilitates the repair process by modulating chromatin structure and recruiting other repair proteins.

Clinical Significance

Mutations in the CHD4 gene have been associated with various human diseases, including cancer. CHD4 is frequently mutated in endometrial cancer, and its dysregulation has been implicated in other malignancies such as breast cancer and colorectal cancer. The role of CHD4 in maintaining genomic stability and regulating gene expression makes it a critical factor in tumorigenesis.

Furthermore, CHD4 mutations have been linked to neurodevelopmental disorders. For instance, mutations in CHD4 can lead to Sifrim-Hitz-Weiss syndrome, a condition characterized by intellectual disability, developmental delay, and distinct facial features.

Structure

CHD4 contains several functional domains that contribute to its activity. These include:

• Chromodomains: Involved in recognizing and binding to methylated histones.
• Helicase domains: Provide ATPase activity necessary for chromatin remodeling.
• DNA-binding domains: Facilitate interaction with DNA.

The combination of these domains allows CHD4 to effectively remodel chromatin and regulate gene expression.

Research

Ongoing research is focused on understanding the precise mechanisms by which CHD4 regulates chromatin structure and gene expression. Studies are also exploring the potential of targeting CHD4 in cancer therapy, given its role in tumorigenesis.

Also see

• Chromatin remodeling
• NuRD complex
• DNA repair
• Gene expression
• Cancer