Purine-Rich Element Binding Protein B (Purβ) is a member of the purine-rich element binding protein family, which plays a crucial role in the regulation of DNA replication and transcription. This protein is known for its ability to bind preferentially to single-stranded purine-rich sequences, which are present at origins of replication and in gene flanking regions across various eukaryotic organisms, from yeasts to humans .
Purβ is characterized by its three single-stranded DNA binding domains, which enable it to interact with specific DNA sequences. These interactions are essential for its role in repressing the transcription of certain genes. For instance, Purβ represses the transcription of the smooth muscle α-actin gene (Acta2) in fibroblasts and smooth muscle cells by binding to single-stranded DNA sequences flanking two 5′ CArG boxes in the Acta2 promoter .
The repressive function of Purβ is mediated through its interaction with other transcription factors. It has been shown to inhibit the coactivator function of myocardin, a potent transcriptional coactivator protein that regulates vascular smooth muscle cell differentiation. Purβ achieves this by forming a complex with myocardin and serum response factor (SRF), thereby preventing the activation of smooth muscle gene transcription .
Research has identified several single-nucleotide polymorphisms (SNPs) in the PURB gene that result in amino acid variants of Purβ. These variants can affect the protein’s repressor activity by altering its interaction with other transcription factors, although they do not significantly impact its ability to bind to purine-rich single-stranded DNA sequences . For example, certain variants exhibit repressor activity that ranges from approximately 1.5-fold greater to 2-fold less than the wild-type Purβ .
Understanding the structure and function of Purβ has significant implications for biomedical research, particularly in the context of cardiovascular diseases. Since Purβ plays a role in regulating the expression of genes involved in smooth muscle cell differentiation, it could be a potential target for therapeutic interventions aimed at treating conditions such as atherosclerosis and other vascular disorders .