ARID1A

ARID1A (AT-Rich Interaction Domain 1A) is a gene that encodes a protein also called ARID1A, a subunit of the SWI/SNF chromatin remodeling complex. The SWI/SNF complex is a multi-subunit complex that utilizes the energy of ATP hydrolysis to disrupt histone-DNA contacts and alter chromatin structure. This remodeling is critical for the regulation of gene expression, DNA repair, and DNA replication.

Function:

The ARID1A protein contains an AT-rich interaction domain (ARID), which is responsible for DNA binding. As a member of the SWI/SNF complex, ARID1A plays a crucial role in regulating gene expression by altering chromatin accessibility. It is involved in numerous cellular processes, including cell growth, differentiation, and development. The SWI/SNF complex can act as both a transcriptional activator and a repressor, depending on the specific context and the genes being regulated.

Clinical Significance:

Mutations in the ARID1A gene are frequently observed in a wide range of human cancers, including ovarian clear cell carcinoma, endometrioid carcinoma, gastric cancer, and colorectal cancer. These mutations often lead to loss of ARID1A protein expression, disrupting the function of the SWI/SNF complex. Loss of ARID1A function is associated with genomic instability, altered gene expression patterns, and increased susceptibility to tumorigenesis. ARID1A loss can impact cancer development, progression, and response to therapy.

Structure:

The ARID1A protein is a large protein with several functional domains, including the ARID domain, which is responsible for DNA binding. The exact structure and interactions of ARID1A within the SWI/SNF complex are still being actively researched.

Related Genes:

The ARID1A gene is part of a family of ARID genes, including ARID1B, ARID2, ARID3A, ARID3B, ARID4A, and ARID4B. These genes encode proteins with similar ARID domains and are involved in various aspects of gene regulation. ARID1B is a closely related paralog of ARID1A and also a subunit of the SWI/SNF complex. Loss-of-function mutations in ARID1B have also been linked to developmental disorders and cancer.