SPI1
Description
The SPI1 (Spi-1 proto-oncogene) is a protein-coding gene located on chromosome 11.
The SPI1 gene encodes the PU.1 transcription factor, which is a crucial regulator of myeloid and B-lymphoid cell development. PU.1 is a nuclear protein that binds to a specific DNA sequence called the PU-box, located on enhancers of target genes, and regulates their expression in coordination with other transcription factors. PU.1 can also influence alternative splicing of target genes. Multiple protein isoforms are encoded by different transcript variants of the SPI1 gene. PU.1 is essential for hematopoiesis and plays a key role in determining cell fate decisions. It interacts with various regulatory factors, including SWI/SNF, TFIID, GATA-2, GATA-1, and c-Jun, influencing its activity and cell fate decisions. PU.1 can modulate the expression of thousands of genes in hematopoietic cells, including cytokines. It is expressed in monocytes, granulocytes, B cells, and NK cells but is absent in T cells, reticulocytes, and megakaryocytes.
SPI1 encodes a pioneer transcription factor that plays a crucial role in hematopoiesis by decompacting stem cell heterochromatin and facilitating access for other transcription factors to previously inaccessible genomic regions. This allows SPI1 to directly regulate gene expression by binding to specific regulatory elements, and indirectly influence transcription by recruiting factors like interferon regulatory factors (IRFs) to these regions. SPI1 is involved in activating genes critical for myeloid and lymphoid lineages, including CSF1R, and collaborates with other transcription factors, such as GATA1, to activate specific genes like FCER1A. SPI1 may be particularly important for the transition from pro-B to pre-B cells. SPI1 binds to the purine-rich DNA sequence 5'-GAGGAA-3', known as the PU-box, through its ETS domain. Studies have shown that SPI1 can bind to RNA in vitro and potentially interfere with pre-mRNA splicing.
SPI1 is also known as AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A.
