Core Binding Factor Beta (CBFβ) is a crucial component of the core-binding transcription factor complex, which plays a significant role in the regulation of gene expression related to hematopoiesis and osteogenesis. The human recombinant form of CBFβ is a synthesized version of this protein, produced through recombinant DNA technology, and is used extensively in research and therapeutic applications.
CBFβ is the beta subunit of the heterodimeric core-binding transcription factor, which also includes an alpha subunit (RUNX1, RUNX2, or RUNX3). Unlike the alpha subunit, CBFβ does not bind directly to DNA. Instead, it enhances the DNA-binding affinity of the alpha subunit, thereby facilitating the transcription of target genes .
CBFβ is involved in the regulation of various genes essential for hematopoiesis (the formation of blood cellular components) and osteogenesis (bone formation). It interacts with the alpha subunit to bind to the core site of various enhancers and promoters, including those of the murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, and GM-CSF promoters .
Mutations and chromosomal rearrangements involving the CBFB gene are associated with several diseases. For instance, a pericentric inversion of chromosome 16 [inv (16) (p13q22)] results in a chimeric transcript that fuses the N terminus of CBFβ with the C-terminal portion of the smooth muscle myosin heavy chain 11. This rearrangement is commonly associated with acute myeloid leukemia (AML) of the M4Eo subtype .
The human recombinant form of CBFβ is produced using recombinant DNA technology. This involves inserting the CBFB gene into an expression vector, which is then introduced into a host cell (such as E. coli or yeast). The host cells are cultured, and the recombinant protein is expressed, harvested, and purified for use in research and therapeutic applications.
CBFβ, as part of the core-binding factor complex, participates in various biochemical interactions. It allosterically enhances the DNA-binding capability of the alpha subunit, allowing the complex to bind to specific DNA sequences and regulate gene transcription. Analytical techniques such as electrophoretic mobility shift assays (EMSAs), chromatin immunoprecipitation (ChIP), and reporter assays are commonly used to study these interactions and the regulatory mechanisms of CBFβ.
The activity of CBFβ is regulated through its interaction with the alpha subunit and other co-factors. Post-translational modifications, such as phosphorylation, can also influence its function. Additionally, the expression of CBFβ is tightly controlled at the transcriptional level, ensuring that it is produced in the right amounts and at the right times during cellular differentiation and development.