Transcription factor PU.1 is a protein that in humans is encoded by the SPI1 gene. This gene encodes an ETS-domain transcription factor that activates gene expression during myeloid and B-lymphoid cell development. The nuclear protein binds to a purine-rich sequence known as the PU-box found on enhancers of target genes, and regulates their expression in coordination with other transcription factors and cofactors. The protein can also regulate alternative splicing of target genes. Multiple transcript variants encoding different isoforms have been found for this gene. The ETS domain is the DNA-binding module of PU.1 and other ETS-family transcription factors.