SPI1

This gene encodes an ETS-domain transcription factor that activates gene expression during myeloid and B-lymphoid cell development.^[6] 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.^[7]

The PU.1 transcription factor is essential for hematopoiesis and cell fate decisions. PU.1 can physically interact with a variety of regulatory factors like SWI/SNF,^[8] TFIID, GATA-2, GATA-1 and c-Jun. The protein-protein interactions between these factors can regulate PU.1-dependent cell fate decisions. PU.1 can modulate the expression of 3000 genes in hematopoietic cells including cytokines. It is expressed in monocytes, granulocytes, B and NK cells but is absent in T cells, reticulocytes and megakaryocytes. Its transcription is regulated by various mechanisms .^[9]

PU.1 is an essential regulator of the pro-fibrotic system. In fibrotic conditions, PU.1 expression is perturbed, resulting in upregulation of fibrosis-associated genes in fibroblasts. Disruption of PU.1 in pro-fibrotic fibroblasts leads to them returning into their resting state. PU.1 is seen to be highly expressed in extracellular matrix-producing pro-fibrotic fibroblasts while it is downregulated in inflammatory/ ECM-degrading and resting fibroblasts. The majority of the cells expressing PU.1 in fibrotic conditions are fibroblasts with a few infiltrating lymphocytes. PU.1 induces the polarization of resting and inflammatory fibroblasts into pro-fibrotic fibroblasts.^[10]

The ETS domain is the DNA-binding module of PU.1 and other ETS-family transcription factors.

SPI1 has been shown to interact with:

• FUS,^[11]
• GATA2,^[12]
• IRF4,^[13][14] and
• NONO.^[15]